Extracorporeal Cardiopulmonary Resuscitation with Therapeutic Hypothermia for Prolonged Refractory In-hospital Cardiac Arrest

Abstract

Background and Objectives

We identified the impact of extracorporeal cardiopulmonary resuscitation (ECPR) followed by therapeutic hypothermia on survival and neurologic outcome in patients with prolonged refractory in-hospital cardiac arrest (IHCA).
Methods

We enrolled 16 adult patients who underwent ECPR followed by therapeutic hypothermia between July 2011 and December 2015, for IHCA. Survival at discharge and cerebral performance category (CPC) scale were evaluated.
Results

All patients received bystander cardiopulmonary resuscitation (CPR); the mean CPR time was 66.5±29.9 minutes, and the minimum value was 39 minutes. Eight patients (50%) were discharged alive with favorable neurologic outcomes (CPC 1–2). The mean follow-up duration was 20.1±24.3 months, and most deaths occurred within 21 days after ECPR; thereafter, no deaths occurred within one year after the procedure.
Conclusion

ECPR followed by therapeutic hypothermia could be considered in prolonged refractory IHCA if bystander-initiated conventional CPR is performed.

Full text

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ABSTRACT
Background and Objectives: We identied the impact of extracorporeal cardiopulmonary
resuscitation (ECPR) followed by therapeutic hypothermia on survival and neurologic
outcome in patients with prolonged refractory in-hospital cardiac arrest (IHCA).
Methods: We enrolled 16 adult patients who underwent ECPR followed by therapeutic
hypothermia between July 2011 and December 2015, for IHCA. Survival at discharge and
cerebral performance category (CPC) scale were evaluated.
Results: All patients received bystander cardiopulmonary resuscitation (CPR); the mean
CPR time was 66.5±29.9 minutes, and the minimum value was 39 minutes. Eight patients
(50%) were discharged alive with favorable neurologic outcomes (CPC 1–2). The mean follow-
up duration was 20.1±24.3 months, and most deaths occurred within 21 days aer ECPR;
thereaer, no deaths occurred within one year aer the procedure.
Conclusion: ECPR followed by therapeutic hypothermia could be considered in prolonged
refractory IHCA if bystander-initiated conventional CPR is performed.
Keywords: Extracorporeal membrane oxygenation; Cardiopulmonary resuscitation;
Hypothermia, induced
INTRODUCTION
Many studies have shown that extracorporeal cardiopulmonary resuscitation (ECPR) has
favorable outcomes for treating cardiac arrest, particularly in-hospital cardiac arrest (IHCA).1-
7) The overall rate of survival at discharge is 32%–45%,1-7) and a favorable neurologic outcome
(cerebral performance category [CPC] of 1 or 2) rate of 77%–100% has been reported among
survivors.2-7) Although these studies might have publication bias, and there is currently
insucient evidence to recommend routine ECPR for cardiac arrest, ECPR could potentially
reverse cardiac arrest if it is rapidly implemented.8) Some reports have shown that rapid
implementation of ECPR was related to favorable outcomes.9-11)
Korean Circ J. 2017 Nov;47(6):e335
https://doi.org/10.4070/kcj.2017.0079
pISSN 1738-5520·eISSN 1738-5555
Original Article
Received: Apr 6, 2017
Revised: Jun 22, 2017
Accepted: Aug 10, 2017
Correspondence to
Wookjin Choi, MD
Department of Emergency Medicine, Ulsan
University Hospital, University of Ulsan College
of Medicine, 877, Bangeojinsunhwando-ro,
Dong-gu, Ulsan 44033, Korea.
Tel: +82-52-250-8507
Fax: +82-52-250-8150
E-mail: koreanermd@gmail.com
Copyright © 2017. The Korean Society of
Cardiology
This is an Open Access article distributed
under the terms of the Creative Commons
Attribution Non-Commercial License (https://
creativecommons.org/licenses/by-nc/4.0)
which permits unrestricted noncommercial
use, distribution, and reproduction in any
medium, provided the original work is properly
cited.
ORCID iDs
Yun Seok Kim
https://orcid.org/0000-0002-2817-557X
Yong Jik Lee
https://orcid.org/0000-0002-0837-4336
Ki-Bum Won
https://orcid.org/0000-0001-5502-9933
Jeong Won Kim
https://orcid.org/0000-0001-7986-9240
Sang Cjeol Lee
https://orcid.org/0000-0003-0502-1022
Chang-Ryul Park
https://orcid.org/0000-0003-2841-7046
Jong-Pil Jung
https://orcid.org/0000-0002-2992-7729
Wookjin Choi
https://orcid.org/0000-0001-8779-0081
Yun Seok Kim , MD1, Yong Jik Lee , MD1, Ki-Bum Won , MD2,
Jeong Won Kim , MD3, Sang Cjeol Lee , MD1, Chang-Ryul Park , MD1,
Jong-Pil Jung , MD1, and Wookjin Choi , MD4
1
Department of Thoracic and Cardiovascular Surgery, Ulsan University Hospital, University of Ulsan College
of Medicine, Ulsan, Korea
2Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
3Department of Thoracic and Cardiovascular Surgery, Andong Hospital, Andong, Korea
4
Department of Emergency Medicine, Ulsan University Hospital, University of Ulsan College of Medicine,
Ulsan, Korea
Extracorporeal Cardiopulmonary
Resuscitation with Therapeutic
Hypothermia for Prolonged Refractory
In-hospital Cardiac Arrest

Conflict of Interest
The authors have no financial conflicts of
interest.
Author Contributions
Conceptualization: Kim YS; Data curation:
Lee YJ; Formal analysis: Won KB; Funding
acquisition: none; Investigation: Kim JW;
Methodology: Lee SC; Project administration:
Choi W; Resources: none; Software: none;
Supervision: Park CR, Jung JP; Validation:
Choi W; Visualization: Won KB; Writing -
original draft: Kim YS; Writing - review &
editing: Choi W.
However, a dedicated ECPR team is essential for rapid implementation of ECPR. Ideally, the
team should be available full-time in the hospital and respond immediately to ECPR calls. At
our institution, there are unfortunately only 2 extracorporeal membrane oxygenation (ECMO)
specialists and 2 perfusionists; therefore, they cannot respond immediately to all ECPR calls.
In this circumstance, the duration of conventional cardiopulmonary resuscitation (CPR) is
usually prolonged, without return of spontaneous circulation (ROSC). This scenario might
be similar in other hospitals worldwide. Therefore, we reviewed the eects of ECPR for
prolonged, refractory IHCA in order to evaluate the survival rate and neurologic outcome of
these patients.
METHODS
Patients
A total of 82 patients underwent ECMO (CAPIOX EBS®; Terumo, Tokyo, Japan) at our
institution between July 2011 and December 2015. Of these, 23 patients underwent ECPR for
IHCA. Among these, we excluded 4 patients who received ECPR immediately aer cardiac
arrest, from an ECMO team that was already activated before the arrest occurred. We excluded
another 3 patients who did not undergo subsequent therapeutic hypothermia. Finally, we
identied 16 patients who met the enrollment criteria (Figure 1). The primary outcome of the
study was in-hospital mortality, and the secondary outcome was 1-year survival.
This study was approved by our Ethics Committee/Institutional Review Board, which waived the
requirement for informed patient consent because of the retrospective nature of the analysis.
Treatment protocol
ECPR is indicated in suspected cardiac arrest if the following criteria are met: 1) age <75 years,
2) no-ow time <5 minutes, and 3) ROSC for less than 30 minutes without uncontrollable
bleeding, previous severe neurologic decit, previous end-stage organ failure, or current
intracranial hemorrhage. These criteria are in alignment with current recommendations12-14)
but are not an absolute indication.
Our ECPR team consists of one cardiac surgeon, one assistant (resident, intern, or nurse), and
one perfusionist. They are not stationed in the hospital but are required to live within 30 minutes
of the hospital. During CPR, an attending physician calls the cardiac surgeon to discuss whether
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ECMO (n=82)
ECMO without arrest (n=59)
Team activation before arrest (n=4)
Therapeutic hypothermia (−) (n=3)
ECPR (n=23)
Team activation after arrest (n=19)
Therapeutic hypothermia (+) (n=16)
Figure 1. Enrollment criteria (July 2011 to December 2015).
ECMO = extracorporeal membrane oxygenation; ECPR = extracorporeal cardiopulmonary resuscitation.

ECPR should be performed, and the surgeon activates the team. While the team arrives, the
physician obtains informed consent for ECPR from the patient's family, if available.
We routinely insert cannulas in the right femoral artery and vein using the percutaneous
technique, with or without ultrasound guidance. We open the le inguinal area and expose
the femoral vessels to insert the cannulas in cases of failed cannulation. Aer guide wire
insertion, 3,000 units of unfractionated heparin are infused intravenously; cannulation
is performed using an 18-Fr arterial cannula (OptiSite®; Edward Lifesciences, Irvine, CA,
USA) and a 20-Fr venous cannula (VFEM®; Edward Lifesciences). The circuit is primed
with normal saline and 1,000 units of unfractionated heparin during cannulation. A chest
radiograph is used to monitor and adjust the venous cannula tip position at the level of the
carina. Transthoracic echocardiography is performed when sucient circulatory support is
established, followed by a coronary angiography or a computed tomography scan, depending
on the suspected cause of arrest.
ECMO target parameters include cases when: 1) the bypass ow is as high as possible if the
drainage is adequate and the cardiac index is usually between 2.0 and 2.8 L/min/m2, 2) mean
arterial pressure between 50 and 70 mmHg, 3) arterial pulse pressure >10 mmHg without
le ventricular distension or pulmonary edema, and 4) decrease and normalization of serum
lactate level. Activated clotting time is maintained between 160 to 200 seconds by adjusting
the intravenous heparin infusion dose. However, in patients with active bleeding, heparin
is discontinued until the bleeding is stopped. If the cannulated limb is pale, we insert a
5-Fr catheter at the cannulated supercial femoral artery for distal perfusion. In the case of
pulmonary edema without pulse pressure, because of severe le ventricular dysfunction,
an intravenous epinephrine infusion is added to facilitate ventricular contraction. Invasive
procedures such as interatrial septostomy or le ventricular venting cannula insertion are not
routinely performed to decompress the le ventricle for patients with contraindications.
Therapeutic hypothermia is routinely performed in unresponsive patients (Glasgow Coma
Score ≤8) with IHCA treated with ECPR. The ECMO machine at our hospital (CAPIOX EBS®;
Terumo) is not equipped with a cooling device, so patients are cooled with an endovascular
cooling catheter (Alsius®; Zoll Medical Corp., Chelmsford, MA, USA) placed in the inferior
vena cava via a femoral venous sheath or cooled with a surface cooling pad device (Arctic
Sun®; Bard Medical, Louisville, CO, USA) applied to the patient's chest and limbs. The
cooling procedure is initiated as soon as the catheter or cooling pad is installed and
continued until the core body temperature reaches 34.5°C–35.0°C. The target temperature
is 34.5°C to avoid overcooling and complications. Shivering during mild therapeutic
hypothermia is evaluated using the Bedside Shivering Assessment Scale, and patients with
a score >1 are treated with deeper sedation or with a bolus of intravenous meperidine and
muscle relaxant in refractory cases.15) The core body temperature is recorded every hour with
a thermometer at the tip of an esophageal probe. Hypothermia is maintained for 48 hours,
and gradual rewarming is initiated. The target rate of rewarming is 0.5°C of temperature
elevation every 12 hours.
ECMO ow is reduced gradually to 1 L/min and maintained for at least 12 hours when
improved cardiac function is conrmed using a transthoracic echocardiography. Heparin
treatment is discontinued, and the cannulas are removed aer 4 to 6 hours if the patient is
hemodynamically stable and the lactate level is not increasing. The cannulas are removed,
and the sites are manually compressed for 1 hour if they are inserted percutaneously;
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however, if the cannulas are inserted through skin incision, they are removed, and the
femoral vessels are repaired surgically using 5-0 monolament non-absorbable sutures.
Statistical analysis
Categorical variables are presented as numbers and percentages and were compared using
the χ2 and Fisher's exact tests. Continuous variables are expressed as the mean±standard
deviation (SD) and were compared using Student's t-test or the Mann-Whitney U test.
The survival rate was estimated with the Kaplan-Meier method. All reported p values were
2-sided, and p<0.05 was considered statistically signicant. SPSS version 19 (SPSS Inc.,
Chicago, IL, USA) was used for statistical analyses.
RESULTS
Baseline patient characteristics
The baseline characteristics of the study population are shown in Table 1. One patient
underwent o-pump coronary artery bypass (OPCAB) graing 2 days prior to the procedure,
for myocardial infarction. All patients received by-stander CPR, and the “no-ow” time (time
between arrest and CPR start) was too short to measure. The mean “low-ow” time (time
between CPR start and bypass start) was 66.5±29.9 minutes, and the minimum value was 39
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Table 1. Baseline characteristics
Characteristics All (n=16) Survivors (n=8) Non-Survivors (n=8) p value
Age (years) 58.2±12.4 55.6±16.0 60.8±7.4 0.24 7
Male sex 10 (62.5) 5 (62.5) 5 (62.5) 1.0
Body surface area (m2) 1.75±0.19 1.76±0.24 1.73±0.13 0.713
Previous medical history
Diabetes mellitus 4 (25.0) 2 (25.0) 2 (25.0) 1.0
Hypertension 6 (37.5) 2 (25.0) 4 (50.0) 0.608
COPD 0 - - -
Chronic liver disease 0 - - -
Chronic kidney disease 0 - - -
Coronary artery disease 6 (37.5) 3 (37.5) 3 (37.5) 1.0
ICMP 2 (12.5) 1 (12.5) 1 (12.5) 1.0
History of cardiac surgery 1 (6.3) 1 (12.5) 0 1.0
Witnessed CPR 16 (100) - - -
Low-flow time*
Total (minutes) 66.5±29.9 63.3±25.1 69.8±35.5 0.600
Without any ROSC (minutes) 47.0±9.8 44.4±9.9 49.6±9.7 0.208
Site of CPR start 0.057
Emergency department 6 (37.5) 5 (62.5) 1 (12.5)
Catheterization room 6 (37.5) 2 (25.0) 4 (50.0)
ICU 2 (12.5) 1 (12.5) 1 (12.5)
OR 1 (6.3) 0 1 (12.5)
General ward 1 (6.3) 0 1 (12.5)
Initial rhythm
VF 6 (37.5) 3 (37.5) 3 (37.5) 1.0
VT 10 (62.5) 5 (62.5) 5 (62.5) 1.0
Pulseless electrical activity 0 - - -
Peak serum pH 7.15±0.14 7.18±0.18 7.14±0.09 0.343
Peak serum lactate (mmol/L) 11.2±3.5 10.6±4.3 11.8±2.6 0.596
Peak serum creatinine (mg/dL) 1.40±0.48 1.24±0.26 1.56±0.61 0.345
Peak serum troponin T (ng/mL) 11.0±16.0 14.6±20.6 7.5±9.7 0.753
COPD = chronic obstructive pulmonary disease; CPR = cardiopulmonary resuscitation; ICMP = ischemic cardiomyopathy; ICU = intensive care unit; OR =
operating room; ROSC = return of spontaneous circulation; VF = ventricular fibrillation; VT = ventricular tachycardia.
*Time between CPR start and bypass start.

minutes. The emergency unit (n=6) and the angiography room (n=6) were the most frequent
ECPR sites. Out of the 2 patients who received ECPR in the intensive care unit (ICU), one
underwent a percutaneous coronar y intervention (PCI) just before the arrest, and the other
underwent OPCAB graing 2 days before ECPR. One patient received ECPR in the operating
room (OR) during the ventilator weaning period aer a rotator-cu surgery. He had received
coronary stenting at the le anterior descending (LAD) branch 5 years prior to undergoing
ECPR. In the general ward, one patient received CPR 18 days aer a ap surgery for diabetic
foot. This patient underwent balloon angioplasties on the le circumex and right coronary
arteries under CPR, followed by ECPR. The baseline characteristics were not dierent
between survivors and non-survivors.
Early outcomes and follow-up
Early outcomes are summarized in Table 2, and all patient clinical data are presented in Table 3.
Myocardial infarction was the most common cause of arrest (87.5%). Mortality primarily
occurred within the third day (75%) of ECPR. A total of 8 patients died before discharge
(mortality group); among them, 7 patients died on ECMO. Of these 7 patients, 3 died on
the day of ECPR, and another 3 died 2 or 3 days aer the procedure. In the mortality group,
a patient (patient 16, Table 3) died from uncontrollable bleeding from the sternotomy site
that was made for central cannulation. The Methods section describes the frequency of
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Table 2. Early ECPR IHCA outcomes
Outcomes All (n=16) Survivors (n=8) Non-survivors (n=8) p value
Cause of arrest
Myocardial infarction 14 (87.5) 7 (87.5) 7 (87.5) 1
Left main culprit lesion 3 (18.8) 1 (12.5) 2 (25.0) 1
Multiple VD 12 (75.0) 5 (62.5) 7 (87.5) 0.569
Pulmonary embolism 1 (6.3) 1 (12.5) 0 1
Fulminant myocarditis 1 (6.3) 0 1 (12.5) 1
Concomitant procedure 15 (93.8) 7 (87.5) 8 (100.0) 1
PCI 13 (81.3) 6 (75.0) 7 (87.5)
Pulmonary thrombolysis 1 (6.3) 1 (12.5) 0
Temporary pacemaker 1 (6.3) - 1 (12.5)
LVEF after ECMO implantation 24.8±14.2 28.1±15.0 21.5±13.4 0.315
CRRT 10 (62.5) 3 (37.5) 7 (87.5) 0.119
ECMO duration (hours) 77.6±62.1 92.9±49.2 62.2±72.9 0.0 74
ECMO weaning off 9 (56.3) 8 (100.0) 1 (12.5) <0.001
ICU stay (days) 11.6±10.2 17.3±9.8 5.9±7.2 0.01 3
Hospital stay (days) 36.3±50.8 67.6±56.8 4.9±7.1 0.002
CPC score 1–2 8 (50.0) 8 (100.0) - -
Causes of death -
No ROSB*3 (18.8) - 3 (37.5)
Vasoplegia*2 (12.5) - 2 (25.0)
Bleeding*1 (6.3) - 1 (12.5)
Sepsis*1 (6.3) - 1 (12.5)
Heart failure†1 (6.3) - 1 (12.5)
Complications
Chronic renal failure 1 (6.3) 1 (12.5) 0 1
Pneumonia 3 (18.8) 2 (25.0) 1 (12.5) 1
Bleeding 1 (6.3) 0 1 (12.5) 1
Limb ischemia 1 (6.3) 1 (12.5) 0 1
Limb contracture 3 (18.8) 3 (37.5) 00.2
Bed sore 1 (6.3) 1 (12.5) 0 1
New onset heart failure 2 (12.5) 2 (25.0) 0 0.467
CPC = cerebral performance category; CRRT = continuous renal replacement therapy; ECMO = extracorporeal membrane oxygenation; ECPR = extracorporeal
cardiopulmonary resuscitation; ICU = intensive care unit; IHCA = in-hospital cardiac arrest; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary
intervention; ROSB = return of spontaneous beating; VD = vessel disease.
*Death on ECMO; †death after ECMO weaning.

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Table 3. Clinical data of all patients
Pt. Age
(years) Sex Diagnosis Initial
rhythm pH*Lactate*Low-flow time
(minutes)
Arrest
locale
Bundle
therapy
ECMO duration
(hours)
ECMO
wean off CRRT Pneumonia New onset
heart failure
Limb
ischemia
Hospital stay
(days) Cause of death
Survival at discharge
1 38 M AMI, 2VD VT 7.24 5.6 83 ER PCI 126 Y N N Y Y 155
2 54 M AMI, 1VD VT 7. 24 4.5 51 ER PCI 9 Y N N N N 13
3 45 M AMI, LM 3VD VT 6.97 9.5 42 ER PCI 55 Y N N N N 17
4 78 F AMI, 3VD VT 7.34 7. 6 54 Angio PCI 147 Y N Y N N 151
571 F AMI, 3VD VF 7.15 15 43 Angio PCI 142 Y Y Y Y N 58
671 FICMP, AMI, LAD
dissect
VF 7.3 8 14.5 102 ICU OPCAB
2 days ago
70 Y Y N N N 72
7 36 M PTE VT 6.85 15 92 ER Pulmonary
thrombolysis
124 Y Y N N N 54
8 52 M AMI, 1VD VF 7.1 9 12.8 39 ER PCI 70 Y N N N N 21
Death before discharge
9 72 M AMI, LM 3VD VT 7.10 7. 6 44 ICU PCI 6 N Y N N N 1 Refractory VT
10 62 M AMI, LM 2VD VT 7.18 10.0 50 OR PCI 62 N Y N N N 3 Vasoplegic shock
11 53 F AMI, 3VD VT 7.1 0 15.0 47 Angio PCI 21 N Y N N N 1 Refractory VT
12 58 F ICMP AMI, 3VD VT 6.98 12.2 45 Angio PCI 51 Y Y N N N 21 Heart failure
13 56 M AMI, 2VD VF 7. 08 13.3 70 Ward PCI 27 N N N N N 1 Refractory VF
14 58 M AMI, 3VD VF 7.3 0 9.5 135 Angio PCI 237 N Y Y N N 9 Sepsis
15 72 M AMI, 2VD VT 7.1 6 11.7 52 Angio PCI 43 N Y N N N 2 Vasoplegic shock
16 55 F Fulminant
myocarditis
VF 7.18 15.0 115 ER Pacemaker 51 N Y N N N 2 Bleeding
AMI = acute myocardial infarction; Angio = angiography room; CPRT = continuous renal replacement therapy; ECMO = extracorporeal membrane oxygenation; ECPR = extracorporeal cardiopulmonary
resuscitation; ER = emergency room; ICMP = ischemic cardiomyopathy; ICU = intensive care unit; LAD = left anterior descending; LM = left main disease; OPCAB = off-pump coronary artery bypass; OR
= operating room; PCI = percutaneous coronary intervention; Pt. = patient; PTE = pulmonary thromboembolism; VD = vessel disease; VF = ventricular fibrillation; VT = ventricular tachycardia.
*Worst value before ECPR.

procedures; invasive procedures such as central ECMO to decompress the le ventricle are
not routinely performed in patients with contraindications. This patient, however, was alert
and young (55-year-old) but showed pulmonary edema and limb ischemia on peripheral
ECMO. Based on this, peripheral ECMO was replaced with central ECMO. Another 58-year-
old female patient (patient 12, Table 3) with ischemic cardiomyopathy (ICMP) was rescued
with ECPR and was weaned o ECMO 51 hours aer. Twenty days later, however, she died
from heart failure, and her family did not want further CPR to be performed.
Eight patients survived to discharge (survival group) with favorable neurologic outcomes
(CPC 1–2). Of these, 7 patients had CPC 1. In the survival group, a patient (patient 1, Table 3)
underwent fasciotomy followed by Achilles tendon lengthening because of limb ischemia,
and another patient (patient 7, Table 3) underwent Achilles tendon lengthening alone
because of ankle contracture. Two patients (patient 1 and 5, Table 3) experienced newly onset
heart failure. Patient 5 died one year aer discharge, and patient 1 is still alive 5 years aer
ECPR and waiting for heart transplantation.
The mean follow-up duration was 20.1±24.3 months, and one patient (patient 5, Table 3)
died one year aer discharge due to heart failure. Most mortality occurred between the day
of and the 21st day aer ECMO implantation, and no mortality occurred within 1 year aer
(Figure 2).
DISCUSSION
We identied the impact of ECPR followed by therapeutic hypothermia on survival and
neurologic outcome in patients with prolonged, refractory IHCA. Rates of survival and poor
neurologic outcome of conventional CPR for patients with IHCA are currently low. Survival to
discharge was 15%, and only 50% of these survivors had favorable neurologic outcomes (CPC
scale 1 or 2).16) However, ECPR was associated with increased survival benets compared with
conventional CPR in patients with IHCA who received refractory to conventional CPR for
more than 10 minutes.5)
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Time (months)
0.6
0.4
0.2
0 2 4 6 8 10 12
Survival
0.8
1.0
Figure 2. Survival curve of patients who received ECPR for prolonged, refractory IHCA.
ECPR = extracorporeal cardiopulmonary resuscitation; IHCA = in-hospital cardiac arrest.

Risk factors associated with in-hospital mortality in ECPR have been reported in previous
studies, including initial rhythm as pulseless electrical activity or asystole, long “low-ow”
time, low serum pH, and high serum lactate.1)3)4) In practice, however, these factors, with
the exception of reducing the “low-ow” time, cannot be controlled by the ECMO team.
Some reports have indicated that rapid implementation of ECPR can improve cardiac
arrest outcomes and can be considered for potentially reversible cardiac arrest if rapidly
implemented.8-11) Kim et al.17) reported that every 10-minute increment in low-ow time
increased the rate of mortality by 5%, and an amount of time less than 60 minutes is
important for improving survival outcomes. Based on these results, they recommended
that the team and machine be prepared to respond rapidly to these events. In the real
world, although it is necessary to have many specialists in the hospital for rapid ECPR
implementation, most institutions cannot aord this stang model. In these circumstances,
the duration of “low-ow” time tends to be prolonged (66.5±29.9 minutes with a minimum
of 39 minutes in our study), even if arrest occurs in the hospital, and it is very dicult to
determine if ECPR should be performed.
A few studies have evaluated the use of therapeutic hypothermia in adult patients that
receive ECPR.2)9)14)18) Based on these studies, therapeutic hypothermia as a bundle therapy is
being established as a recommended procedure.19) However, the ideal target temperature,
initiation, and duration of therapeutic hypothermia for treating patients who received ECPR
for IHCA have not been well-established. We selected a target temperature of 34.5°C to avoid
unexpected bleeding complications, while still maintaining the neuroprotective eect of mild
therapeutic hypothermia.20)
In this study, we worked to reect realistic clinical scenarios from team activation to the
start of bypass and excluded 4 patients who received ECPR immediately aer cardiac arrest
from an ECMO team that was already activated before the arrest occurred. As mentioned
previously, we have 2 ECPR teams, and each consists of one cardiac surgeon, one assistant
(resident, intern, or nurse), and one perfusionist. The teams are not stationed in the hospital
but live within 30 minutes travel time from the hospital. Under these circumstances, the
“low-ow” time in our study was relatively long (66.5±29.9 minutes with a minimum of 39
minutes), but the rate of survival to discharge with a favorable neurologic outcome (50%) was
comparable with other reports.1-5)9-11) In our experience, it usually takes about 20 minutes to
prepare the machine and perform cannulation, but we were unable to measure the exact time
because of insucient medical records.
The most common cause of mortality was failure to achieve return of spontaneous beating
aer the bypass was started (37.5%). All of these patients (n=3) died within the rst 27
hours aer the procedure because heart transplantation or a ventricular assist device was
not available, and there were no other options except termination of ECMO. The mean
“low-ow” time in patients who died from failure to achieve return of spontaneous beating
was 53.7±14.2 minutes, and this result was not signicant compared with the mean “low-
ow” time for the other patients (69.5±32.1 minutes). The severity and extent of myocardial
damage are more important risk factors for failing to achieve return of spontaneous beating
than the duration of “low-ow” time. However, we were unable analyze this result because of
the small population and retrospective design of this study.
As mentioned above, some risk factors associated with in-hospital mortality have been
reported in previous studies, including initial rhythm as pulseless electrical activity or
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asystole, long “low-ow” time, low serum pH, and high serum lactate.1)3)4) In our study,
however, the severity of lactic acidosis and duration of “low-ow” time were not identied as
risk factors for in-hospital mortality. This might be attributable to the small study population
and retrospective design of this study.
This study is limited by the retrospective analyses of observational data and only included 16
patients and no control group, so a comparative study could not be performed. Therefore, these
results did not completely show the eectiveness of therapeutic hypothermia or ECPR. The
decision to implement ECPR was aected by the attending physician's preference, producing
selection bias. Further prospective studies with larger cohorts are needed to conrm our results.
In conclusion, ECPR in combination with therapeutic hypothermia could be considered in
prolonged refractory IHCA if bystander-initiated conventional CPR is performed, even if the
team does not reside in the hospital.
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