**7. Complications**

ECPR, like all other forms of extracorporeal life support, is associated with a host of mechanical and non-mechanical complications. Frequency and severity

for most ECPR-specific complications are not reported in the literature at this time –reports generally include all ECMO patients as a single group. The ELSO website has a comprehensive list of reported ECMO and ECPR complications, including mechanical, neurologic, cardiovascular, infectious, immunologic, hematologic, metabolic, pulmonary, and renal [53].

Here we will highlight some of the better studied complications.

#### **7.1 Neurologic complications**

Neurologic complications on ECMO have been extensively documented due to their significant burden and influence on outcomes. In pediatric patients treated with ECMO, there is a 7% prevalence of intracranial hemorrhages and a 6% prevalence of cerebral infarctions. Overall ECMO survival drops by half in patients who develop neurological injury. Survivors have multiple long-term morbidities, including seizures and global developmental delay.

ECPR specific neurologic injuries are more prevalent and more significant than with routine ECMO. The ELSO database reports 12% incidence of seizures, 11.8% incidence of hemorrhage or infarct, and 11% incidence of brain death. Hemorrhages and infarcts were associated with lower survival. Severe acidosis, non-cardiac arrest etiology, and on ECMO CPR were risk factors for the neurologic injuries. Unfortunately, registry datasets are not granular and more specific associations are difficult to identify.

Literature reporting of neurodevelopmental outcomes post ECMO and ECPR is limited, and there is a varied approach to assessment and documentation [54]. However, overall trends appear encouraging. Favorable neurologic outcomes have been shown in up-to 65% of ECPR survivors. Favorable outcomes in these reports are defined as normal function or mild cerebral disability, showing that a good quality of life is attainable for arrest patients treated with ECPR. Further work is needed to uncover determinants of good outcomes.

#### **7.2 Acute kidney injury and renal replacement therapy**

Acute kidney injury (AKI) is common in critically ill patients, and patients treated with ECMO are especially prone to developing AKI. ECMO patients with AKI and subsequent fluid overload have a higher risk of longer ECMO runs and greater mortality [7]. Fluid overload management differs between centers, and includes fluid restriction, diuresis, slow continuous ultrafiltration (SCUF). None of these methods are efficient in removing solutes, and so continuous renal replacement therapy may be needed when fluid overload coincides with AKI. It should be noted that aggressive early CRRT may be associated with worse outcome [55], and indicates that judicious fluid management must always be an ongoing balance tailored to each patient.

#### **8. Outcomes**

ECPR is superior to conventional CPR. Overall survival to discharge in pediatric patients treated with ECPR in the ELSO registry is approximately 40%; **Table 5** shows a breakdown of this data. Other reports of ECPR survival vary across the literature, and the quoted numbers range between 23%-55%. In contrast, overall reported survival rates for conventional CPR in pediatrics range between 16 to 30%. The large range of variability is due to differences between institutional experience, expertise, and reporting on these patients. Superior survival rates persist with longer term follow-up and have been demonstrated up-to 12 months after discharge.

**135**

**Table 5.**

*ECPR runs per the ELSO database, 1990–2018 [56].*

therapy [59].

*Extracorporeal Cardiopulmonary Resuscitation DOI: http://dx.doi.org/10.5772/intechopen.83658*

score matching for patients across these groups.

**8.1 Determining outcomes**

A major indicator of quality of life in survivors of ECPR is neurologic outcome. While work is limited, there is indication that these outcomes may be positive, and perhaps better than in patients rescued by conventional CPR. Several reviews have shown that survival with minimal neurologic damage was more frequent in patients rescued with ECPR. This trend remained true even after performing propensity

Several pre-ECMO factors have been identified as important to determining outcomes of ECPR. Disease process leading to arrest is one such factor. Post-cardiac surgery patients, or patients who arrest in the setting of another primary cardiac process, have consistently demonstrated the best survival when rescued with ECPR versus conventional CPR. Patients who arrest in the setting of neonatal respiratory disease also have favorable outcomes. Patients who arrest in the setting of sepsis have higher mortality rates than patients with a pure cardiac process, but have better survival than if managed with CPR alone [57]. Patients with arrest in the setting of a respiratory illness also do well [58]. Patients with gastrointestinal conditions, who are usually patients with complex multiorgan disorders, tend to have worse outcomes. Patients with oncologic disease and other immunosuppressed processes also do worse [15]. Time to full support is another important predictor of survival of patients rescued with ECPR [17]. Longer time spent in a low flow state is associated with drastic drops on survival to hospital discharge. Post-discharge, patients with longer low flow times have worse neurologic outcomes and higher post-discharge mortality. Duration in a low flow state is a highly modifiable factor, and should be minimized in order to achieve the best outcomes. It is important to establish ECMO candidacy for all high risk patients, so that ECMO can be deployed quickly in the setting of an arrest. In centers that offer ECPR, a rapid response team must be available at all times, in order to minimize the time needed to establish ECMO flow. This team must be highly trained and very adaptable, highlighting the need for an ongoing development program for any center that offers ECPR. In addition to the presence of a rapid response team, ECMO equipment must be readily available for utilization at all times. During the resuscitation, pauses in compressions are needed to allow for cannula insertion. Duration and frequency of such pauses must be limited as much as possible, since any no-flow time dramatically decreases survival as well. It is important to note that prolonged resuscitation may not be futile if ECPR is utilized, highlighting the importance of choosing the right patients for ECPR

Location of arrest can influence survival. Arrests that occur in the intensive care unit, have the best outcomes post management with ECPR. Outside the intensive care unit, outcomes worsen, perhaps related to the quality of resuscitation provided and the duration it may take to establish access for ECMO. Locations where ECPR can be offered will be dependent on institutional logistics and resource availability. Regardless, there should be advance coordination to ensure the equipment and

Neonatal ECPR 1718 1140 (66%) 708 (41%) Pediatric ECPR 3946 2262 (57%) 1675 (42%) Total 5664 3402 (60%) 2383 (42%)

**Total runs Survive ECLS Survival to discharge**

A major indicator of quality of life in survivors of ECPR is neurologic outcome. While work is limited, there is indication that these outcomes may be positive, and perhaps better than in patients rescued by conventional CPR. Several reviews have shown that survival with minimal neurologic damage was more frequent in patients rescued with ECPR. This trend remained true even after performing propensity score matching for patients across these groups.

#### **8.1 Determining outcomes**

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

metabolic, pulmonary, and renal [53].

ing seizures and global developmental delay.

needed to uncover determinants of good outcomes.

**7.2 Acute kidney injury and renal replacement therapy**

**7.1 Neurologic complications**

for most ECPR-specific complications are not reported in the literature at this time –reports generally include all ECMO patients as a single group. The ELSO website has a comprehensive list of reported ECMO and ECPR complications, including mechanical, neurologic, cardiovascular, infectious, immunologic, hematologic,

Neurologic complications on ECMO have been extensively documented due to their significant burden and influence on outcomes. In pediatric patients treated with ECMO, there is a 7% prevalence of intracranial hemorrhages and a 6% prevalence of cerebral infarctions. Overall ECMO survival drops by half in patients who develop neurological injury. Survivors have multiple long-term morbidities, includ-

ECPR specific neurologic injuries are more prevalent and more significant than with routine ECMO. The ELSO database reports 12% incidence of seizures, 11.8% incidence of hemorrhage or infarct, and 11% incidence of brain death. Hemorrhages and infarcts were associated with lower survival. Severe acidosis, non-cardiac arrest etiology, and on ECMO CPR were risk factors for the neurologic injuries. Unfortunately, registry datasets

Literature reporting of neurodevelopmental outcomes post ECMO and ECPR is limited, and there is a varied approach to assessment and documentation [54]. However, overall trends appear encouraging. Favorable neurologic outcomes have been shown in up-to 65% of ECPR survivors. Favorable outcomes in these reports are defined as normal function or mild cerebral disability, showing that a good quality of life is attainable for arrest patients treated with ECPR. Further work is

Acute kidney injury (AKI) is common in critically ill patients, and patients treated with ECMO are especially prone to developing AKI. ECMO patients with AKI and subsequent fluid overload have a higher risk of longer ECMO runs and greater mortality [7]. Fluid overload management differs between centers, and includes fluid restriction, diuresis, slow continuous ultrafiltration (SCUF). None of these methods are efficient in removing solutes, and so continuous renal replacement therapy may be needed when fluid overload coincides with AKI. It should be noted that aggressive early CRRT may be associated with worse outcome [55], and indicates that judicious fluid management must always be an ongoing balance tailored to each patient.

ECPR is superior to conventional CPR. Overall survival to discharge in pediatric patients treated with ECPR in the ELSO registry is approximately 40%; **Table 5** shows a breakdown of this data. Other reports of ECPR survival vary across the literature, and the quoted numbers range between 23%-55%. In contrast, overall reported survival rates for conventional CPR in pediatrics range between 16 to 30%. The large range of variability is due to differences between institutional experience, expertise, and reporting on these patients. Superior survival rates persist with longer term follow-up and have been demonstrated

Here we will highlight some of the better studied complications.

are not granular and more specific associations are difficult to identify.

**134**

**8. Outcomes**

up-to 12 months after discharge.

Several pre-ECMO factors have been identified as important to determining outcomes of ECPR. Disease process leading to arrest is one such factor. Post-cardiac surgery patients, or patients who arrest in the setting of another primary cardiac process, have consistently demonstrated the best survival when rescued with ECPR versus conventional CPR. Patients who arrest in the setting of neonatal respiratory disease also have favorable outcomes. Patients who arrest in the setting of sepsis have higher mortality rates than patients with a pure cardiac process, but have better survival than if managed with CPR alone [57]. Patients with arrest in the setting of a respiratory illness also do well [58]. Patients with gastrointestinal conditions, who are usually patients with complex multiorgan disorders, tend to have worse outcomes. Patients with oncologic disease and other immunosuppressed processes also do worse [15].

Time to full support is another important predictor of survival of patients rescued with ECPR [17]. Longer time spent in a low flow state is associated with drastic drops on survival to hospital discharge. Post-discharge, patients with longer low flow times have worse neurologic outcomes and higher post-discharge mortality. Duration in a low flow state is a highly modifiable factor, and should be minimized in order to achieve the best outcomes. It is important to establish ECMO candidacy for all high risk patients, so that ECMO can be deployed quickly in the setting of an arrest. In centers that offer ECPR, a rapid response team must be available at all times, in order to minimize the time needed to establish ECMO flow. This team must be highly trained and very adaptable, highlighting the need for an ongoing development program for any center that offers ECPR. In addition to the presence of a rapid response team, ECMO equipment must be readily available for utilization at all times. During the resuscitation, pauses in compressions are needed to allow for cannula insertion. Duration and frequency of such pauses must be limited as much as possible, since any no-flow time dramatically decreases survival as well.

It is important to note that prolonged resuscitation may not be futile if ECPR is utilized, highlighting the importance of choosing the right patients for ECPR therapy [59].

Location of arrest can influence survival. Arrests that occur in the intensive care unit, have the best outcomes post management with ECPR. Outside the intensive care unit, outcomes worsen, perhaps related to the quality of resuscitation provided and the duration it may take to establish access for ECMO. Locations where ECPR can be offered will be dependent on institutional logistics and resource availability. Regardless, there should be advance coordination to ensure the equipment and


#### **Table 5.**

*ECPR runs per the ELSO database, 1990–2018 [56].*

personnel needed can be deployed smoothly. Literature has shown that it is possible to successfully offer ECPR in the emergency department with such arrangements.

On-ECMO complications also influence survival, regardless whether it is a planned run or ECPR [57]. Neurologic complications are associated with high mortality post-ECPR. Inability to achieve and maintain adequate perfusion while on ECMO, noted by metabolic and lactic acidosis, has been tied to worse outcomes [60, 61]. Similarly, cardiac arrest during the ECMO run is also associated with poor outcomes. Renal failure and the need for renal replacement therapy have an association with inferior outcomes [58]. Severe coagulopathy and DIC also worsen survival – maintaining anticoagulation for the circuit and avoidance of fatal hemorrhage is a fine balance, and coagulopathy raises the risk of fatal hemorrhages [16, 62].

### **9. Special mention: out-of-hospital ECPR**

Out of hospital cardiac arrests (OHCA) have very high mortality rates and very poor neurologic outcomes for both pediatric and adult patients [63, 64]. As a result, there has been growing interest in applying ECPR to OHCA. Overall survival rates vary for OHCA ECPR. Reported survival rates range from 12 to 30%, but patient numbers are very limited and there is extreme selection bias in this cohort [4]. ELSO reports that about half of all OHCA ECPR were reported in Europe, followed by the Asia-Pacific region, and lastly North America [65]. Almost all published experience is exclusively adult experience [66].

Application of ECPR for OHCA varies across different centers. Some institutions provide a "scoop and run" strategy, with quick transport to the emergency department for cannulation in select patients with OHCA [67]. Other centers have a different approach, with the ability to "stay and treat" by initiating ECPR on the scene of the OHCA [68]. The different styles of application are dependent on availability of resources, feasibility, and local experience.

Provision of ECPR to OHCA presents challenges with cost-effectiveness, optimal candidacy, and timing of deployment. However, if done in settings with the appropriate resources utilizing an aggressive strategy with optimum patient selection, survival can possibly be favorable [14]. However, evidence remains inconclusive and requires further study [66].

#### **10. Conclusion and future directions**

ECPR has emerged as an exciting rescue therapy, promising to improve outcomes of cardiac arrest. It has shown superiority over conventional CPR, with better survival to discharge and better longer-term survival. It has also shown better neurologic outcomes. As overall experience grows, we expect to see increased uses and even better outcomes.

Nonetheless, this is an emerging field and there is a lot left to learn. Especially in pediatrics, knowledge gaps include:

	- a.Definition of refractory arrest, i.e. how long should conventional CPR continue before ECPR should be considered

**137**

**Author details**

Abdelaziz Farhat1

Dallas, TX, USA

provided the original work is properly cited.

*Extracorporeal Cardiopulmonary Resuscitation DOI: http://dx.doi.org/10.5772/intechopen.83658*

tency to decrease low flow time

c.Inclusion and exclusion criteria for out-of-hospital cardiac arrest

3.Optimal approach to comprehensive post arrest care for ECPR patients

At this time, most ECMO and ECPR research is observational in nature. Generalization of pediatric data is hindered by the heterogeneity of patient ages and diagnosis, as well as variability of practice between different institutions. Because of the small numbers of patients overall and per institution, the field is ripe with opportunity for collaborative work. International registries and large research collaboratives may be able to provide enough patients to power larger investigations. More data will help empower decisions to treat children with ECPR, refine the

caliber of care they receive, and improve their future quality of life.

\*, Cindy Darnell Bowens1

4.Approach to neuroprotection and neuroprognostication post-ECPR

2.Team preparedness: specific nature of training to maintain ECPR team compe-

5.Functional and neurodevelopmental post-discharge status of patients rescued

d.Assessment of futility in possible ECPR candidates

with ECPR, and how to improve such outcomes

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

1 Children's Medical Center and University of Texas Southwestern Medical Center,

2 Children's Hospital Boston and the Harvard Medical School, Boston, MA, USA

\*Address all correspondence to: abdelaziz.farhat@utsouthwestern.edu

, Ravi Thiagarajan2

and Lakshmi Raman1

b.Inclusion and exclusion criteria for higher risk populations, including immunosuppressed patients and trauma patients

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

coagulopathy raises the risk of fatal hemorrhages [16, 62].

**9. Special mention: out-of-hospital ECPR**

experience is exclusively adult experience [66].

of resources, feasibility, and local experience.

sive and requires further study [66].

and even better outcomes.

pediatrics, knowledge gaps include:

before ECPR should be considered

immunosuppressed patients and trauma patients

1.Ideal ECPR candidacy

**10. Conclusion and future directions**

personnel needed can be deployed smoothly. Literature has shown that it is possible to successfully offer ECPR in the emergency department with such arrangements. On-ECMO complications also influence survival, regardless whether it is a planned run or ECPR [57]. Neurologic complications are associated with high mortality post-ECPR. Inability to achieve and maintain adequate perfusion while on ECMO, noted by metabolic and lactic acidosis, has been tied to worse outcomes [60, 61]. Similarly, cardiac arrest during the ECMO run is also associated with poor outcomes. Renal failure and the need for renal replacement therapy have an association with inferior outcomes [58]. Severe coagulopathy and DIC also worsen survival – maintaining anticoagulation for the circuit and avoidance of fatal hemorrhage is a fine balance, and

Out of hospital cardiac arrests (OHCA) have very high mortality rates and very poor neurologic outcomes for both pediatric and adult patients [63, 64]. As a result, there has been growing interest in applying ECPR to OHCA. Overall survival rates vary for OHCA ECPR. Reported survival rates range from 12 to 30%, but patient numbers are very limited and there is extreme selection bias in this cohort [4]. ELSO reports that about half of all OHCA ECPR were reported in Europe, followed by the Asia-Pacific region, and lastly North America [65]. Almost all published

Application of ECPR for OHCA varies across different centers. Some institutions provide a "scoop and run" strategy, with quick transport to the emergency department for cannulation in select patients with OHCA [67]. Other centers have a different approach, with the ability to "stay and treat" by initiating ECPR on the scene of the OHCA [68]. The different styles of application are dependent on availability

Provision of ECPR to OHCA presents challenges with cost-effectiveness, optimal candidacy, and timing of deployment. However, if done in settings with the appropriate resources utilizing an aggressive strategy with optimum patient selection, survival can possibly be favorable [14]. However, evidence remains inconclu-

ECPR has emerged as an exciting rescue therapy, promising to improve outcomes of cardiac arrest. It has shown superiority over conventional CPR, with better survival to discharge and better longer-term survival. It has also shown better neurologic outcomes. As overall experience grows, we expect to see increased uses

Nonetheless, this is an emerging field and there is a lot left to learn. Especially in

a.Definition of refractory arrest, i.e. how long should conventional CPR continue

b.Inclusion and exclusion criteria for higher risk populations, including

**136**


At this time, most ECMO and ECPR research is observational in nature. Generalization of pediatric data is hindered by the heterogeneity of patient ages and diagnosis, as well as variability of practice between different institutions. Because of the small numbers of patients overall and per institution, the field is ripe with opportunity for collaborative work. International registries and large research collaboratives may be able to provide enough patients to power larger investigations. More data will help empower decisions to treat children with ECPR, refine the caliber of care they receive, and improve their future quality of life.
