Extracorporeal Life Support: Experience with 2,000 Patients : ASAIO Journal

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Extracorporeal Life Support

Experience with 2,000 Patients

Gray, Brian W.*; Haft, Jonathan W.; Hirsch, Jennifer C.; Annich, Gail M.; Hirschl, Ronald B.*; Bartlett, Robert H.*

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ASAIO Journal 61(1):p 2-7, January/February 2015. | DOI: 10.1097/MAT.0000000000000150
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Extracorporeal life support (ECLS) also known as extracorporeal membrane oxygenation (ECMO) has been used to treat critically ill patients with respiratory and cardiovascular failure for more than 4 decades. Hill et al.1 published the first successful use of ECLS in 1972 in a trauma patient who developed acute respiratory distress syndrome (ARDS). This was followed by the first successful use of ECLS in cardiogenic shock in 19732 and newborn respiratory failure in 1975. Since that time, the use of ECLS has been validated as a life-saving therapy,3,4 and centers with expertise in ECLS have grown worldwide through international collaborative efforts. In addition to the dissemination of ECLS around the globe, the indications for ECLS use have expanded over the years from neonatal respiratory failure to its use during extracorporeal cardiopulmonary resuscitation (ECPR).

There have been several large series of ECLS patients reported from centers around the world. Groups from Europe, Asia, and Australia have published studies examining a few dozen to several hundred patients at a time.4–7 However, the University of Michigan Hospital, in Ann Arbor, Michigan, has treated the largest number of patients with ECLS the world over. We previously reviewed and presented the results of the first 1,000 patients treated with ECLS at the University of Michigan.8 The aim of this report is to present the next set of 1,000 patients treated with ECLS at the University of Michigan in combination with and in comparison to the first 1,000 patients, with a unique perspective on the evolving use of ECLS more than the past 4 decades.


We reviewed the data on 2,000 consecutive patients treated with ECLS by the University of Michigan ECMO team from 1972 to 2010. The data were collected prospectively at the time of treatment using the Extracorporeal Life Support Organization (ELSO) registry forms and computer database.9 There are currently nearly 60,000 cases in the total worldwide ELSO registry. We focused on the differences between the first and second 1,000 patients to gain a better understanding of our ECLS experience more than 4 decades.

Basic statistics were performed using SPSS version 17 software package (IBM, Chicago, IL), and tests included the t-test for Equality of Means and the Pearson χ2 test. Significance was defined as p < 0.05.


The first 1,000 patients in this group were previously reported in detail by Bartlett et al.8 They were treated between 1972 and 1998 (26 years). The second group of patients was treated between 1998 and 2010 (12 years).

Survival by Diagnosis

The ECLS survival was 64%. The growth and distribution of cases are presented in Table 1. Since 1998, the greatest areas of growth in ECLS use have been cardiac failure, adult respiratory failure, and the emergence of ECPR.

The distribution of indications for ECLS use and survival is outlined in Table 1. Survival was significantly better in the first 1,000 patients than those treated after 1998 (74% vs. 55%, p < 0.01). Between the first and second 1,000 patients, the proportion of neonates treated for respiratory failure decreased (n = 586 vs. 213), and this group had a significant decrease in survival (88% vs. 72%, p < 0.01). The greatest drops in neonatal respiratory survival were seen in the diaphragmatic hernia and “other” groups. The “other” group is defined as those with rare indications that cannot be placed in any of the larger categories. Median oxygenation index (OI: FiO2 × mean airway pressure ÷ PaO2) was similar among the neonatal respiratory patients in the first and second 1,000 groups (42 vs. 40, p = 0.62). Oxygenation index in survivors was significantly lower than in those who died (48 ± 32 vs. 56 ± 35, p = 0.02).

Table 1:
Survival Outcomes of 2,000 Extracorporeal Life Support Patients

Survival increased in the pediatric respiratory group from 70% to 84% (p < 0.01), with greatest increases in those with pneumonia and ARDS. Median OI was also similar over time in this group (41 vs. 40, p = 0.53), and mean OI was again higher in those who died (42 ± 20 vs. 50 ± 31, p = 0.05).

Adults with respiratory failure increased more than 40%. Although absolute survival rate in this group was greater after 1998, the difference was not statistically significant (46% vs. 52%, p = 0.33). The distribution of diagnoses and survival of the adult respiratory group are shown in Table 1.

There was a substantial increase in the use of ECLS for cardiac failure in both pediatric and adult patients (136 vs. 344), but survival was nearly identical overall (44% vs. 43%, p = 0.84). As an adjunct to ECLS for cardiac failure, ECPR emerged since 1998 as a heroic measure to save moribund patients in cardiopulmonary arrest. As of 2010, there were 129 patients in our series, with a 41% survival rate. The incidence and survival in the adult and pediatric populations were nearly identical, as seen in Table 1.

The database did not prospectively record the exact cause of death. However, in our experience, most deaths occurred due to lack of improvement of primary disease on ECLS, multisystem organ failure, sepsis, or loss of central nervous system (CNS) function.

Patient and Extracorporeal Life Support Run Characteristics

There was very little change in pre-ECLS ventilator days in any group, with the neonatal respiratory and adult cardiac groups with the shortest duration and pediatric respiratory group having the longest (Table 2). The mean duration of ECLS increased from 5.8 to 7.7 days in neonatal patients, decreased from 12.8 to 8.6 in pediatric patients, and decreased from 10.4 to 7.3 in adult respiratory patients (p < 0.01 in all groups).

Table 2:
Extracorporeal Life Support Run Characteristics in 2,000 Patients

The cannulation mode for ECLS stayed relatively stable in all groups, based on the physiologic derangement specific to each group (Table 2). The majority of cardiac and ECPR patients were supported with veno-arterial (VA)-ECLS, and there was increased usage of the venovenous (VV) mode after 1998 because of the availability of double lumen cannulas for children and adults.

Multiple ECLS runs were conducted in 92 patients, with 35% survival. Six of these patients were supported with ECLS three times, with 17% survival. The most frequent group placed on ECLS multiple times was the pediatric cardiac group (n = 27), with an overall survival of 26%.


The most common complication was nonintracranial bleeding, usually associated with cannula insertion sites, in 39% of patients. Renal failure defined as the need for dialysis or hemofiltration was the second most common complication at 31%. The least common complications were pump malfunction (2%), air entry into the circuit (8%), and intracranial bleeding or infarction (8%). The complications associated with the greatest survival were air entry into the circuit (71%) and blood clots in the circuit (62%); those associated with poorest survival were pump malfunction (36%), need for dialysis (38%), and cardiac arrhythmia (39%).

The neonatal respiratory failure group had lower incidence than the other patient groups in all complication categories other than clots in the circuit. Intracranial bleeding occurred in less than 10% of patients in all groups other than the ECPR group. Arrhythmias occurred most frequently in the cardiac failure patients and adults with respiratory failure. New infection while on circuit was most common in the pediatric and adult respiratory patients, and survival was less than 50% in most categories of patients who developed an infection. Mechanical complications were relatively rare. The lowest incidence was pump malfunction, but patients with this complication had particularly poor survival in all but the neonatal and pediatric respiratory groups. There was low incidence of cannula-related complications, and this was associated with variable survival (Tables 3 and 4).

Table 3:
Complications in 2,000 Respiratory Extracorporeal Life Support Patients
Table 4:
Complications in 2,000 Cardiac Extracorporeal Life Support Patients


Our data reveal decreased survival over time, with the only significant increase in survival coming in the pediatric respiratory group. In the first 1,000 patient group, a large subsection of patients were neonatal respiratory patients with meconium aspiration, infant respiratory distress, and sepsis (40%) who have been shown to have remarkable survival as a result of ECLS treatment (92%).9 The use of ECPR in the late 1990s added a new subset of patients with a predisposition toward poorer survival. In our experience, early successes using ECLS have led to increased use in patients who would have historically been too ill for ECLS. This is perhaps the reason for decreased survival in neonatal respiratory patients with diaphragmatic hernia and “other” diagnoses in the second group. Oxygenation Index is a measure that has been named as a predictor for mortality in neonates and children with respiratory distress.10 Median pre-ECLS OI was similar between these groups in our study, likely due to the recognized benefit of ECLS once OI reaches 40.

Due to our studies and others,3,10 ECLS has become an accepted therapeutic modality for use in treating neonates with respiratory failure, particularly those children with meconium aspiration, respiratory distress, and sepsis. Extracorporeal gas exchange allows time for the lungs to heal from the physiologic insult, resulting in excellent survival that has remained at greater than 90%. Patients with congenital diaphragmatic hernia (CDH) and persistent pulmonary hypertension, however, tend to have greater physiologic derangements at baseline, resulting in more modest survival. In our study, survival slightly decreased over time, likely due to a sicker patient population being placed on ECLS.

Advances in pulmonary treatment modalities such as inhaled nitric oxide, inhaled surfactant, and high-frequency oscillatory ventilation have led to less need for the more invasive ECLS while maintaining equivalent survival.11,12 We saw virtually no change in the modality of ECLS, even with the demonstration of efficacy of the venovenous modality and equivalent survival in the neonatal population.13,14

Pediatric respiratory patients had increased survival in the later patient group. Similar to the neonatal group, a survival advantage has been shown with ECLS over conventional treatment in severe respiratory failure.15 Pre-ECLS factors associated with mortality have included OI, pediatric risk of mortality score, PaCO2, and shock.15 Patients who died had higher mean OI, representing severity of respiratory failure.

ECLS survival decreased with renal failure (serum creatinine >3.0 mg/dl), failure to return the patient to dry weight, and the use of inotropes.16 Due to these findings, we began to employ the early use of continuous renal replacement therapy for pediatric ECLS patients with signs of renal failure in our treatment algorithm. Patients in the second 1,000 group who underwent hemodialysis or had elevated serum creatinine had increased survival over renal failure in the first 1,000 patients. Since 2008, we have decreased sedation which allowed spontaneous breathing,17,18 and applied ECMO before salvage status. Along with advances in ECLS technology, these factors have helped to decrease mortality in pediatric respiratory failure patients treated with ECLS.

Other trends over time included increasing use of the venovenous modality, likely due to the advent and efficacy of dual-lumen venous cannulas.19 Patients spent less time on ECLS, possibly representing the success of multimodality treatment and decreased pulmonary injury in the pre-ECLS time period.

Despite controversy in the critical care community on the indications for and efficacy of ECLS in adult respiratory failure patients, its use in this population is increasing in frequency. There have been several cohort and case–control studies that mostly examined ECLS use in ARDS patients, including one from our group, showing survival to discharge in the range of 50–66%.20–22 The most robust trial in support of ECLS in the adult respiratory failure group was the Comparisson of ECMO to StandardCare in Acute Respiratory Failure (CESAR) trial from the United Kingdom that showed in a prospective randomized multicenter fashion that transfer to care in an ECLS capable center was superior to care at a center without ECLS expertise.4

From the first to the second 1,000 set of ECLS patients, we saw an increasing proportion of adults treated for respiratory failure, and with this came a trend toward increased survival in both the pneumonia and the ARDS groups, reflecting patient selection and improving ECLS treatment strategies for the patient as a whole. This improved survival has led to maintaining patients with severe pulmonary failure on ECLS for prolonged durations while awaiting lung recovery. Our group published the account of a patient who survived for 53 days on VV-ECLS after suffering from severe ARDS.23

As in the pediatric respiratory group, we observed decreased ECLS duration and an increasing trend toward the use of VV-ECLS. The standard cannulation mode for adults with respiratory failure is VV-ECLS, and the efficacy of dual-lumen right internal jugular venous cannulation has encouraged the use of VV-ECLS in practice.24–27 VA cannulation in respiratory failure is now reserved for those in refractory shock or concomitant cardiac failure.

ECLS for adult respiratory failure came into the international spotlight during the influenza A(H1N1) pandemic of 2009. The pandemic struck first during winter in the Southern Hemisphere, where the Australia and New Zealand (ANZ) ECMO Influenza Investigators published an account of their robust experience using ECLS to treat H1N1 patients.28 The ANZ ECMO group placed 68 patients on ECLS and had a 71% survival to intensive care unit (ICU) discharge. The work of the ANZ ECMO group served as a guide for intensivists in the Northern Hemisphere in the mobilization of ECLS teams to prepare for the spread of the H1N1 pandemic in the coming winter. Many groups in Europe, Asia, and the United States published their experience, adding to the worldwide catalog of ECLS in the face of H1N1 influenza.29–32

Our group saw adult respiratory ECLS cases increase from 6 in 2008 to 24 in 2009. This number regressed to seven cases in 2010. In the end, this new worldwide fund of knowledge allowed for a greater understanding of the use of ECLS to treat H1N1, use of ECLS in general, and the mobilization of hospital resources to accommodate the sudden demand for ECLS.33,34

The number of pediatric cardiac cases doubled in the second 1,000 patients (105–256) but the survival stayed the same (48% vs. 44%). Until recently, ECLS was the only mechanical life support system for children with profound cardiogenic shock. The main application has been in cardiac failure immediately after cardiac operations, within minutes or hours of coming off cardiopulmonary bypass. In 2013, the pediatric Berlin Heart Ventricular Assist Device (VAD) became available. The Food and Drug Administration (FDA) qualifying trial for the Berlin Heart was a matched pairs study, matching to the ELSO pediatric cardiac database.35 The number of myocarditis and cardiomyopathy cases increased in the second 1,000 patients, as we learned that the survival is quite good in that condition (50–60%).

The number of adult cardiac cases doubled in the second 1,000 cases (31–88), and survival increased from 33% to 40%. Unlike pediatric cardiac ECLS, adult patients can proceed to VAD and ultimately transplant. This algorithm has evolved in our center.36 VA ECLS is used as the first mechanical support, at times after failing on intraaortic balloon pump. If CNS function is good and there are no other contraindications, we then proceed to VAD implantation with the intent of chronic support until transplantation.

In the first 1,000 patients, VA ECLS was sometimes used for patients who arrested as preparations were underway for cannulation. These cases are counted only as respiratory or cardiac cases. Beginning in 1999, the category of ECPR was instituted to identify patients who were in unexpected cardiac arrest, CPR was underway, and VA ECLS was added as an adjunct to CPR. This occurred rarely because the circuit must be primed with cannulation possible within a few minutes of onset of CPR. The survival rate is 41%, much better than CPR alone (<10%).37 The survival rate is essentially those patients who regain both cardiac and brain function.


Major concerns for complications for all patients treated with ECLS continue to revolve around the extremes of the coagulation cascade, manifesting as thrombosis in the circuit, intracranial hemorrhage/infarction, and bleeding. To this end, laboratories have been researching nonthrombogenic surfaces to obviate the need for anticoagulation. These range from heparin-coated circuit surfaces38 to nitric oxide-eluting surfaces.39

Overall Outcome

The decrease in survival rate between the first 1,000 patients (74%) and the second 1,000 patients (55%) is a reflection of the types of patients and the severity of illness in the two groups. The first 1,000 patients were primarily newborn infants with respiratory failure (88% survival) with little cardiac failure and almost no ECPR. In the second 1,000 patients, the newborn respiratory failure was 72% and most of those were diaphragmatic hernia patients who have a worse prognosis because of pulmonary hypoplasia. Since 2000, we have expanded ECLS for severe cardiac and pulmonary failure in children and adults. These patients have a worse prognosis than newborns because of the increased incidence of irreversible heart or lung failure. We added ECPR cases that have a high incidence of irreversible brain injury. Concomitant with a raise in the severity of disease has been the steady improvement of the devices, methods of anticoagulation, and better understanding of cardiac and respiratory management on ECLS, leading to 55% survival. There is much room for improvement.


In 2010, we began using the next generation of ECMO devices (so-called ECMO2). These devices make ECLS much simpler, safer, more automatic, and decrease the need for anticoagulation. ECLS can be managed by the ICU nursing staff, rather than the continuous attendance of an ECMO specialist. The cost and ease of application are improving. We will see how these changes affect the patient groups and outcome in the next 1,000 patients.


Our first 1,000 ECLS patients were managed more than 26 years and were predominantly newborn respiratory failure who rarely have irreversible injury. The survival rate was 74%. The next 1,000 patients we managed more than 12 years and the survival rate was 55%. In the second 1,000 patients, the indications were expanded to children and adults with cardiac and pulmonary failure including patients in ECPR.

ECLS is a mature technology which is used for temporary life support in patients with a high risk of dying (70–80%).3,4,8,13,15,17,40 In the last 1,000 patients, ECLS resulted in 70–80% survival in neonates and children, 50% in adults with respiratory failure, and 40% in patients with cardiac failure.


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extracorporeal membrane oxygenation; extracorporeal circulation; cardiac failure; respiratory failure

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