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Original Articles: Adult Cardiac

Extracorporeal Membrane Oxygenation to Support Cardiopulmonary Resuscitation in Adults

^a Department of Cardiology, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
^b Department of Pediatric Critical Care Medicine, Children's Hospital and Regional Medical Center and the University of Washington, Seattle, Washington
^c Extracorporeal Life Support Organization, University of Michigan, Ann Arbor, Michigan
^d Department of Pediatrics, University of Utah, and Primary Children's Medical Center, Salt Lake City, Utah

Accepted for publication December 24, 2008.

^_* Address correspondence to Dr Thiagarajan, Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115 (Email: ravi.thiagarajan{at}cardio.chboston.org).

This article has been selected for the open discussion forum on the CTSNet Web Site: http://www.ctsnet.org/sections/newsandviews/discussions/index.html

 

	Abstract

Top Abstract Introduction Material and Methods Results Comment References

 
Background: Extracorporeal membrane oxygenation (ECMO) to support cardiopulmonary resuscitation (CPR) has been shown to improve survival in children and adults. We describe outcomes after the use of ECMO to support CPR (E-CPR) in adults using multiinstitutional data from the Extracorporeal Life Support Organization (ELSO) registry.

Methods: Patients greater than 18 years of age using ECMO to support CPR (E-CPR) during 1992 to 2007 were extracted from the ELSO registry and analyzed.

Results: Two hundred and ninety-seven (11% of 2,633 adult ECMO uses) reports of E-CPR use in 295 patients were analyzed. Median age was 52 years (interquartile range [IQR], 35, 64) and most patients had cardiac disease (n = 221; 75%). Survival to hospital discharge was 27%. Brain death occurred in 61 (28%) of nonsurvivors. In a multivariate logistic regression model, pre-ECMO factors including a diagnosis of acute myocarditis (odds ratio [OR]: 0.18; 95% confidence interval [CI]: 0.05 to 0.69) compared with noncardiac diagnoses and use of percutaneous cannulation technique (OR: 0.42; 95% CI: 0.21 to 0.87) lowered odds of mortality, whereas a lower pre-ECMO arterial blood partial pressure of oxygen (PaO ₂ ) less than 70 mm Hg (OR: 2.7; 95% CI: 1.21 to 6.07) compared with a Pa O ₂ of 149 mm Hg or greater increased odds of mortality. The need for renal replacement therapy during ECMO increased odds of mortality (OR: 2.41; 95% CI: 1.34 to 4.34).

Conclusions: The use of E-CPR was associated with survival in 27% of adults with cardiac arrest facing imminent mortality. Further studies are warranted to evaluate and better define patients who may benefit from E-CPR.

Extracorporeal membrane oxygenation (ECMO) to provide cardiopulmonary support during in-hospital cardiac arrest after conventional cardiopulmonary resuscitation (CPR) has failed to establish an adequate circulation has been shown to promote survival in select children and adults [1–11]. Survival after E-CPR is variably reported, and because maintaining an E-CPR team is expensive, not universally available, and the benefits of E-CPR largely unproven in adults, it is important to better understand survival outcomes among adult patients to recommend its use. However, the ability to understand the use and efficacy of E-CPR is limited because most reports on E-CPR are hampered by small sample size, narrow diagnosis groups, and single institution reports, making generalization difficult.

The goals of this study are to describe demographic characteristics, evaluate techniques employed, and report survival outcomes for adults supported with E-CPR, using multiinstitutional data from the Extracorporeal Life Support Organization (ELSO). In addition, we evaluated demographic characteristics, ECMO support-related features, and also ECMO complications associated with survival after E-CPR use in an attempt to define patients most likely to benefit from E-CPR use.

	Material and Methods

Top Abstract Introduction Material and Methods Results Comment References

 
The ELSO registry collects data on ECMO used to support cardiorespiratory function in children and adults from 116 United States and international centers [12]. Data are reported to registry after approval by the local Institutional Review Boards (IRBs). Waiver of individual patient consent for data reporting is governed by local IRBs and thus is institution specific. A data use agreement between ELSO and member centers allows ELSO to release limited deidentified datasets to the member centers for purposes of analysis for scientific publication and waives the need for approval from individual reporting member centers. Data are reported using a standardized data collection sheet. The registry defines E-CPR as the following: "extracorporeal life support (ECLS) used as part of initial resuscitation from cardiac arrest. Patients who are hemodynamically unstable and placed on ECLS without cardiac arrest are not considered E-CPR" [1].

We included data from all E-CPR runs reported to the registry for patients 18 or greater years of age during 1992 to 2007. Variables used included patient age, diagnosis and procedure codes, type and duration of ECMO support, pre-ECMO mechanical ventilator and patient support details, lowest pre-ECMO arterial blood gas values in the six hours before ECMO, ECMO complications, and in-hospital mortality. Decisions regarding patient selection, cannulation technique, and management of ECMO patients are not standardized, and therefore subject to wide practice variability. Data regarding duration of CPR prior to ECMO, initial cardiac arrest rhythm, and neurologic outcomes for E-CPR survivors are not reported to ELSO and could not used in these analyses.

Data Categorization
Primary and secondary diagnosis (International Classification of Disease-9 CM [ICD-9CM]) and procedure (common procedural terminology [CPT]) codes were used to create diagnostic groups including the following: (1) "cardiac disease" with subcategories of "acute myocardial infarction/ischemia," "acute myocarditis," "cardiomyopathy," "acute pulmonary embolism," and "other cardiac diseases" containing those with primary pulmonary hypertension, congenital heart disease, arrhythmias, and cardiac diagnosis that could not be classified in the other cardiac subcategories; (2) "respiratory disease" including patients with acute respiratory failure and pneumonia; (3) "accidental injury" including trauma, drowning or hypothermia; (4) "sepsis"; and (5) "miscellaneous," including patients who had a diagnosis of cardiac arrest but no other supporting diagnosis codes and other diagnosis that could not be categorized into the other main diagnostic categories.

Patient complications during ECMO were grouped using complication codes created by the ELSO registry into the following categories and subcategories: (1) "ECMO circuit complications" included mechanical failures of the ECMO circuit, clots in the ECMO circuit, air embolus, cannula site bleeding, and surgical bleeding; (2) "central nervous system (CNS) complications" included seizures (clinical or electroencephalogram evidence of seizures), cerebral infarction and intracranial hemorrhage determined by radiologic imaging evidence (computerized tomography) and brain death; (3) "cardiac complications" included cardiac arrhythmias that required treatment, cardiac tamponade, and CPR on ECMO; (4) "pulmonary complications" included pneumothorax requiring treatment and pulmonary hemorrhage; (5) "infectious complications" defined as culture proven infection; (6) "metabolic complications" included arterial blood pH less than 7.2 (metabolic acidosis), blood glucose less than 40 mg/dL (hypoglycemia) and greater than 240 mg/dL (hyperglycemia) while on ECMO; (6) "gastrointestinal complications" included gastrointestinal hemorrhage requiring treatment and hyperbilirubinemia (defined as total serum bilirubin > 15 mg/dL or direct bilirubin > 2 mg/dL); and (7) "renal complications" included serum creatinine greater than 1.5 to 3.0 mg/dL, serum creatinine greater than 3 mg/dL, and receipt of dialysis (hemodialysis or continuous arteriovenous hemodialysis [CAVHD]).

Statistical Analysis
Survival to hospital discharge was defined as discharge from the ECMO center to either home or to another facility. For patients (n = 2) who had multiple ECMO runs only data from the index run were used in the analysis. Demographic, pre-ECMO and ECMO support details and ECMO complications were compared for survivors and nonsurvivors. The Mann-Whitney U test was used for continuous data, while categoric data were compared using the Pearson ² test. The Fisher exact test was used when expected counts in greater than 20% of cells were less than 5. Trends in the utilization of E-CPR and survival after E-CPR use were compared using the Mantel-Haenszel ² for linear association.

Two multivariate logistic regression models were developed to independently evaluate the association of pre-ECMO and ECMO related factors with hospital death. The first model evaluated the association of in-hospital mortality with demographic and pre-ECMO factors and the other model was used to evaluate the association of ECMO factors and complications with hospital death after E-CPR use. Candidate variables for inclusion in a multivariate logistic regression models were selected from the univariate analysis comparing survivors and nonsurvivors. All variables with a univariate p value of less than 0.1 were selected as candidate variables for inclusion in the multivariate model. A forward selection procedure was used for entry of candidate variables into the model. A candidate variable was retained in the multivariable model as a predictor if the p value was 0.05 or less. Variables containing continuous data not meeting the linearity assumption were divided into categories for inclusion in the final logistic regression model. Because some diagnosis groups were small and experienced similar survival, patients with respiratory failure, sepsis, accidental injury, and miscellaneous causes of arrest were combined as "noncardiac group" for inclusion in the logistic regression model. Cases containing missing data were not included in the multivariate models using listwise deletion. The SPSS version 16.0 software (SPSS Inc, Chicago, IL) was used for the analysis. Statistical significance was set at a p value less than 0.05.

	Results

Top Abstract Introduction Material and Methods Results Comment References

 
Study Population
Two hundred and ninety-five patients underwent 297 E-CPR runs during the study period. This constituted 11% of 2,633 adult ECMO uses reported to ELSO during the same time period. Seventy-nine patients (27%) survived to hospital discharge. The median age of E-CPR patients was 52 years (interquartile range [IQR]: 35, 64). The majority of patients had cardiac disease (n = 221, 75%) and received venoarterial ECMO support (n = 269, 91%). The most common vascular access sites for ECMO cannulation included the femoral artery (n = 240; 81%) and femoral vein (n = 206, 70%). The median duration of ECMO support was 67 hours (IQR: 21, 133). The E-CPR use increased over time (Mantel-Haenszel ² p value for linear association < 0.001; Fig 1). However, there was a statistically significant trend towards decreased survival over time (Mantel-Haenszel ² p value for linear association = 0.04; Fig 2).

View larger version (35K): [in this window] [in a new window]   Fig 1. Trends in extracorporeal membrane oxygenation to aid cardiopulmonary resuscitation (E-CPR) utilization in adults. ( = E-CPR cases; = non-E-CPR cases.)

View larger version (30K): [in this window] [in a new window]   Fig 2. Trends in survival rate for adult extracorporeal membrane oxygenation (ECMO) to aid cardiopulmonary resuscitation users. ( = survivors; = nonsurvivors.)

ECMO Complications
The details of ECMO complications in survivors and nonsurvivors are shown in Table 3. The incidence of brain death, persistent metabolic acidosis (arterial blood pH < 7.2) on ECMO support, hyperbilirubinemia, and need for dialysis was higher in nonsurvivors compared with survivors.

Central Nervous System Injury in E-CPR Users
Ninety-eight (33%) patients suffered CNS injury manifest by seizure, radiologic imaging evidence of intracranial bleeding or stroke, or brain death. The incidence of CNS injury was higher in nonsurvivors compared with survivors (42% vs 10%, p < 0.001). The most common form of CNS injury was brain death (n = 61 [21%]). The incidence of brain death was highest in the recent years 2004 to 2007 (26%) compared with patients undergoing ECMO during 1992 to 1999 (16%) and 2000 to 2003 (13%; p = 0.03). Pre-ECMO PaO ₂ (55[37 – 80] vs 77[48 – 170] mm Hg; p = 0.003) was lower for patients who were diagnosed with brain death compared with all other patients. In addition, fewer patients cannulated using percutaneous technique compared with surgical technique (11% vs 26%; p = 0.004) and right internal jugular vein compared with other sites (7% vs 24%; p = 0.01) were diagnosed with brain death.

	Comment

Top Abstract Introduction Material and Methods Results Comment References

 
In this study of adult patients with cardiac arrest receiving CPR, the use of E-CPR was associated with 27% survival to hospital discharge. Survival to hospital discharge was associated with patient diagnosis, higher pre-ECMO arterial blood PaO ₂, the use of percutaneous ECMO cannulation technique, and absence of ECMO complications.

Survival was improved in a subset of patients with acute myocarditis compared with the noncardiac diagnosis group. However, the number of patients with acute viral myocarditis was very small, and thus findings regarding the survival of E-CPR in these patients are preliminary and warrant further study.

Survival to hospital discharge for adult in-patient cardiac arrest resuscitated with conventional CPR therapies has been shown to be poor [13–15]. A report of adult in-hospital cardiac arrest outcomes from the National Registry of Cardiopulmonary Resuscitation containing data from 14,720 events reported a survival rate of 17% [14]. Factors associated with mortality prior to hospital discharge in these patients included patient age greater than 60 years, underlying primary disease, cardiac asystole or pulseless electrical activity as the initial rhythm, absence of severe comorbidities, location of cardiac arrest outside of monitored environments, cardiac arrests occurring during regular working hours, and quality of CPR administered [13–19]. Although we found a higher survival rate of 27% for patients using E-CPR compared with the survival rate reported for those using conventional CPR, the retrospective nature of our study limits our ability to draw conclusions regarding the efficacy of E-CPR compared with standard CPR. In addition, the survival rate for patients using E-CPR may have been confounded by the increased incidence of factors associated with survival for all cardiac arrest patients among adult E-CPR patients. These factors, including the patient location at the time of arrest, cause, initial cardiac arrest rhythm, or CPR management, were not collected by the ELSO registry and thus not available for analysis. However, ECMO support is commonly used when patients fail conventional therapies to support cardiorespiratory function during critical illness and the mortality risk high. A recent report by Chen and colleagues [11] showed that use of E-CPR improved both short and long-term outcomes among adults with witnessed in-hospital cardiac arrest of cardiac origin failing to establish an adequate circulation with greater than 10 minutes of conventional CPR. Thus the use of E-CPR can be considered in adults with in-hospital cardiac arrest when conventional CPR has failed to establish an adequate circulation to promote survival.

The survival to hospital discharge rate for E-CPR users reported here is consistent with other reports [1–11, 20]. Chen and colleagues [9] reported a 32% survival rate among 57 adults with a cardiac disease using E-CPR for cardiac arrest that failed to respond to conventional CPR. In a second report from the same group evaluating E-CPR in 30 patients with acute myocardial infarction, they reported a survival to discharge rate of 48% [10]. Ruttman and colleagues [6] described the use of E-CPR in 25 patients with accidental hypothermia and reported a (36%) survival to hospital discharge. Younger and colleagues [7] described the use of E-CPR in 25 patients with multiple diagnoses (17 [68%] had cardiac disease) receiving CPR in the emergency department and in-hospital, reporting a survival to discharge rate of 36%. Megarbane and colleagues [8] evaluated the use of E-CPR to support refractory cardiac arrest in 17 patients in a medical intensive care unit and reported a lower survival rate of 24%. The lower survival rate in this report was thought to be related to the fact that many patients had out-of-hospital cardiac arrests and needed prolonged CPR (median duration 120 minutes [range, 60 to 180]) prior to ECMO deployment.

The use of E-CPR in adults has increased over time without improvement in survival with increasing experience. In fact, we found a significant trend toward increased mortality in the recent years. This may have resulted from both the increasing use and the inclusion of patients with a variety of underlying diagnoses for E-CPR support. Hence it seemed important to define a population or a diagnosis group that may benefit the most from E-CPR use from this cohort as well as published reports on E-CPR use. From the reports reviewed here, factors associated with improved survival for E-CPR patients included shorter duration of CPR, primary cardiac diagnosis, in-hospital cardiac arrest, reversible reason for cardiac arrest, cause of cardiac arrest amenable to interventions such as coronary revascularization in patients with myocardial infarction, absence of lactic acidosis prior to ECMO, and absence of ECMO complications such as renal failure, multisystem organ failure, and neurologic injury [7–10]. We did not find an independent association of survival with a diagnosis of cardiac disease. However, we found that a small subset of patients with cardiac disease, namely acute viral myocarditis, had improved survival compared with those with noncardiac disease. Improved survival in these patients was possibly related to the presence of single organ disease and overall better prognosis from their primary disease compared with other diagnosis groups [21]. We did not find pre-ECMO arterial blood pH, a surrogate of metabolic acidosis, to be predictive of survival in our analysis. Although not independently associated with survival, we found lower survival rates in patients in the highest age quartile (> 64 years). Similar to these reports and with other uses of ECMO we found that renal failure requiring renal replacement therapy and CNS injury on ECMO predicted poor survival [22]. Based on the prior reports and from our analysis, it appears that young patients with in-hospital cardiac arrest who received short duration of CPR and did not have severe metabolic acidosis may have the best benefit from E-CPR. Finally, the association of short CPR duration and survival indicated that institutions wishing to provide ECMO deployment to aid failed CPR should have readily available skilled personnel to assemble the ECMO circuit and deploy ECMO support at all times. The presence of well-trained and experienced E-CPR teams in some centers may explain the higher survival rates reported by these centers. The ELSO does not provide information on ECMO center characteristics to further evaluate this issue.

We found the association of the use of percutaneous cannulation technique and survival interesting. We speculate that improved survival with percutaneous cannulation may have been due to decreased time to establish vascular access for ECMO institution, resulting in shortened CPR time. In addition, percutaneous cannulation may have led to fewer interruptions in CPR compared with surgical cannulation technique (peripheral vessel or thoracic), where CPR may have been interrupted for identification and cannulation of vascular structures and thus improved survival [1, 23]. The ELSO does not release information about center characteristics and cannulation technique employed may have varied by center.

Neurologic injury during ECMO precludes good outcomes among patients who use ECMO support for any indication [24]. In patients using E-CPR, the risk of CNS injury from CPR may be added to the risk of CNS injury posed by ECMO support. In this analysis we found that 33% E-CPR users had CNS injury and 21% met criteria for brain death. Patients meeting brain death criteria were withdrawn from ECMO sooner than the rest of the cohort. Brain death in these patients likely occurred during CPR rather than injury from the short duration of ECMO use; however, this is not certain. We expected use of the internal jugular vein and the carotid arteries would be associated with a higher incidence of brain death. However, we found the contrary and cannot explain this finding. The use of the internal jugular vein may have been a surrogate for rapid ECMO cannulation because of uncomplicated anatomy resulting in decreased duration of CPR and better CNS outcomes. Although some reports reviewed here indicated good long-term functional outcomes for E-CPR patients surviving to hospital discharge these data were not collected by ELSO, and thus could not be used in our analysis to evaluate neurologic outcomes for adult E-CPR users.

Several important limitations should be considered when interpreting information regarding adult E-CPR outcomes from this analysis. The most significant limitation is the lack of short-term and long-term functional and neurologic outcome data for E-CPR users, which limits evaluation of efficacy. Another significant limitation is the use of retrospective data for this analysis, which precludes accurate assessment of the most proximate cause of cardiac arrest. Furthermore, data reported to ELSO on E-CPR patients do not contain specific information regarding CPR technique, duration of CPR, medications used during CPR, or the use of hypothermia to evaluate the influence of CPR-related factors on survival after E-CPR. In addition, these analyses are limited by lack of data on arterial vascular injury due to ECMO cannulation and data on the number of patients listed or received heart transplantation or bridged to a ventricular assist device. Missing data preclude the use of some variables in multivariable analysis resulting in the loss of important information. Despite these limitations, this is the first large epidemiological study, to our knowledge, describing the use of E-CPR in adults and could inform future evaluation of this therapy and research on improving survival outcomes in adult E-CPR users.

In conclusion, we found that 27% of adults using E-CPR after cardiac arrest survived. Further research should be focused on evaluating short-term and long-term functional neurologic outcomes to better evaluate the future use of this therapy.

	References

Top Abstract Introduction Material and Methods Results Comment References

 

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This Article Abstract Full Text (PDF) Online Discussion Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Peter C. Laussen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thiagarajan, R. R. Articles by Bratton, S. L. Search for Related Content PubMed Articles by Thiagarajan, R. R. Articles by Bratton, S. L. Related Collections Extracorporeal circulation Related Article