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Ann Thorac Surg 2005;79:178-183
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Back from Irreversibility: Extracorporeal Life Support for Prolonged Cardiac Arrest

^a Departments of Thoracic and Cardiovascular Surgery, University Hospital, Caen France
^b Anesthesiology, University Hospital, Caen France
^c Cardiology, University Hospital, Caen France
^d Emergency and Critical Care Medicine, University Hospital, Caen, France

Accepted for publication June 21, 2004.

^* Address reprint requests to Dr Massetti, Department of Thoracic and Cardiovascular Surgery, University Hospital, 14033 Caen, France (E-mail: massetti-m{at}chu-caen.fr).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Conclusion Acknowledgments References

 
BACKGROUND: The survival of patients after prolonged cardiac arrest is still inadequate. Extracorporeal life support (ECLS) represents an alternative therapeutic method for patients who do not respond to conventional cardiopulmonary cerebral resuscitation. This technology is used to support the circulation of a patient with severe cardiac failure.

METHODS: Between June 1997 and January 2003, 40 ECLS procedures were performed in patients who presented with refractory cardiac arrest. During external cardiac massage, the patient was connected to an extracorporeal circuit by the insertion of an arterial and venous cannula through the femoral vessels. The extracorporeal circuit included a centrifugal pump and an oxygenator. Mean age was 42 ± 15 years; the average time of external cardiac massage was 105 ± 44 minutes.

RESULTS: Once the circulation was restored, 22 patients were disconnected from the extracorporeal circulation because of brain death or multiorgan failure; after 24 hours, among the 18 survivors, 6 were weaned off the pump, 9 were bridged to a ventricular assist device, and 2 patients were directly bridged to cardiac transplantation. Eight patients are alive and without any sequelae at 18 month's follow-up.

CONCLUSIONS: In prolonged cardiac arrest with failing conventional measures, rescue by extracorporeal support provides an ultimate therapeutic option with a good outcome in survivors. Our results encourage the wider application of ECLS for refractory cardiocirculatory arrest in selected patients. The high rate of neurologic death needs further improvements in the early phase of resuscitation maneuvers.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment Conclusion Acknowledgments References

 
Worldwide experience with cardiopulmonary resuscitation (CPR) has demonstrated that survival to discharge ranged from 8.2% to 22% in hospitalized patients and was below 3% in out-of-hospital patients who experienced cardiac arrest [1–2]. Because of the low survival rate after prolonged CPR, methods that are more aggressive have been suggested to increase success.

Extracorporeal life support (ECLS) refers to a technology that is used to support the circulation of a patient with severe cardiac failure. The physiologic objective is to provide temporary circulatory support to the vital organs and to unload the failing heart as the injured myocardium attempts to recover. Indications for applying rescue ECLS have not been clearly defined; however, guidelines have been established to avoid futile efforts [3–6].

Portable cardiopulmonary bypass (CPB) is a simple and effective system for controlling a patient's circulatory and respiratory functions on an emergency basis until physicians evaluate the cause of the patient's hemodynamic shock and initiate further treatment [8, 9]. Because this technology made consistent progress with miniaturized pumps and circuit biocompatibility, cardiothoracic surgeons and ECLS specialists have renewed their interest in the use of CPB as an emergency resuscitative tool for patients suffering from refractory cardiac arrest. Published series have demonstrated an overall survival rate of between 15% and 60% in this heterogeneous category of patients [4–11]. To evaluate the impact of ECLS on the survival of patients who experienced a prolonged cardiac arrest, we retrospectively analyzed our experience.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Conclusion Acknowledgments References

 
We reviewed the case histories of all patients treated with emergency CPB for prolonged cardiopulmonary arrest at the University Hospital of Caen between June 1997 and January 2003. Data collection was both retrospective and concurrent. The tracking of each patient's clinical course during the hospitalization was recorded. Vascular, neurologic, hemorrhagic, renal, and perfusion system complications were documented. We selected patients whose conditions leading to CPR were thought to be of cardiac origin. ECLS contraindications included previous irreversible brain damage, terminal malignancy, and age of more than 75 years. Patients receiving ECLS support for weaning from CPB, accidental hypothermia, or for respiratory support were excluded. Briefly, patients were included into the ECLS therapy if they:

• presented with refractory cardiac arrest requiring external cardiac massage;

• could not be returned to spontaneous circulation within 45 minutes;

• received ECLS in the hospital.

In ECLS-supported patients, we selected three groups and analyzed the population data, survival at 24 hours, and weaning from ECLS followed by discharge from the hospital. The group "survival at 24 hours" identified those patients who survived to cardiopulmonary resuscitation-advanced life support and showed no signs of irreversible brain damage.

Device Description
The hardware for emergent cardiopulmonary circulation consisted of a Biomedicus portable bypass system (PBS) (Medtronic, Inc, Minneapolis, MN) incorporating a centrifugal pump console and a water pump system. A preconnected tubing set was attached to a hollow-fiber membrane oxygenator with an integral heat exchanger (Maxima PRF, Medtronic, Inc), a constrained vortex pump chamber, and a flow probe. The ECLS circuit consisted of a closed Carmeda Bioactive Surface-coated circuit of polyvinyl chloride tubing (Medtronic, Inc). Cannulas used were Biomedicus (17F to 25F), according to the size of patients.

Cannulation Technique
Once the decision to use ECLS support has been made, the surgeon dissects the femoral vessels to the groin. Meanwhile, the perfusionist assembles a circuit that meets the specific requirements of the patient's size and primes it with Ringer's lactate solution. Heparin 50 UI/kg is administered intravenously to the patient immediately before cannulation of the vessels. Reinjection of a low dose of heparin allows the activated clotting time (ACT) to be kept at between 150 and 180 seconds at full flow.

Cannulation is peripheral (femorofemoral) using Biomedicus Carmeda BioActive Surface-coated extracorporeal membrane oxygenation cannulas (Medtronic, Inc) placed into the femoral vessels through a modified Seldinger technique (surgical cut-down followed by vessel puncture). The distal tip of the arterial cannula is positioned in the common iliac artery or distal abdominal aorta. The distal tip of the venous cannula is placed in the right atrium under echocardiography guidance and confirmed by chest radiography. Limb ischemia used to be the major problem at the beginning of our experience; therefore, perfusion of the distal limb is accomplished with a small 8F catheter. This arterial shunt is instituted between the side port of the arterial cannula and a point located some centimeters distally in the superficial femoral artery.

Successful ECLS is defined as mean blood pressure of at least 60 mm Hg and flows of at least 2.5 L/m². The Biomedicus pump rpm is increased to approximately 2,500 rpm maximum or until desired flows are obtained. Vasopressor (norepinephrine) is infused to maintain a mean systemic arterial pressure of more than 60 to 70 mm Hg. Ventricular filling and inotropic support maintain a pulsatile flow through the native heart. The aim is to decompress the left heart and to minimize stasis and therefore the risk of intracardiac clot.

To accomplish mechanical decompression of the left heart, we recently performed an atrial balloon septostomy in one patient. A contralateral femoral vein approach was used in which transseptal puncture, followed by blade septostomy, was performed under combined radioscopy and echocardiographic guidance. Sequential balloon inflations were carried out to achieve left heart decompression that was confirmed by echocardiography.

A pulmonary artery catheter is positioned in patients without any evidence of coagulopathy. Depending on myocardial contractility, inotropic support is reduced to decrease myocardial oxygen demand and facilitate recovery. A low tidal volume (5 to 6 mL/kg) of mechanical ventilation with positive end-expiratory pressure at 8 to 10 cm H₂O is applied to fight hydrostatic pressure that is due to postcapillary hypertension and to minimize pulmonary hemorrhage. All patients are anticoagulated with heparin as early as possible to reach an ACT of approximately 160 to 180 seconds at full flow assistance, and an ACT of more than 200 seconds when flow is reduced below 1.5 L/min during the weaning phase.

Management in the Intensive Care Unit
The perfusionist operates the Biomedicus pump initially, and once the patient is stabilized, the intensive care unit (ICU) nurses monitor the pump function. At that time, a perfusionist is available for occasional monitoring visits and emergencies. Continuous venovenous hemofiltration is used to regulate intravascular volume and overall fluid balance and to enable the administration of blood products without induction of volume overload. Transesophageal echocardiography is used serially to enable the assessment of progressive myocardial recovery and to exclude intracardiac clot or other abnormalities.

Biomedicus pump heads are changed if there is evidence of high plasma free hemoglobin on ECLS. The entire circuit is usually changed when an oxygenator change out is required, for example, if plasma water drips from the Maxima Carmeda-coated oxygenator into the gas phase.

The postresuscitation neurologic state is assessed clinically by awaking patients. In case of coma, serial electroencephalogram (EEG) and transcranial Doppler ultrasound is performed.

Weaning
The decision to discontinue ECLS support is based upon combined criteria. The weaning protocol is performed by the assessment of hemodynamic profile and myocardial function under echocardiography during the progressive reduction of pump flow to 500 mL/min. During this period, the anticoagulation is adapted to adequate values of ACT (250 to 300 seconds). Weaning of ECLS is performed if the left ventricular ejection fraction is stable (> 50%). Echocardiographic assessment of myocardial function remains, in our experience, the most important predictor of successful weaning from ECLS.

ECLS is terminated in the absence of an efficient cardiac function recovery or when cardiac transplantation or bridge to another mechanical device cannot be considered (futility criteria). Termination of ECLS is considered when there is evidence of multiorgan failure, overwhelming sepsis, or profound neurologic impact.

The neurologic outcome at hospital discharge was assessed according to the cerebral performance class (CPC) categories of:

1 good cerebral performance,

2 moderate cerebral disability,

3 severe cerebral disability,

4 coma or vegetative state, or

5 brain death or death.

Data Analysis
Values of continuous variables are expressed as means ± standard deviation. Comparison of means was performed using the independent sample t test and Mann-Whitney test for nonparametric data. In addition, a two-tailed p value of less than 0.05 was considered to indicate statistical significance.

	Results

Top Abstract Introduction Patients and Methods Results Comment Conclusion Acknowledgments References

 
Forty patients were treated after meeting the inclusion criteria in this study; patient characteristics are shown in Table 1. All received ECLS during external cardiac massage, and the main indications for ECLS support are listed in Table 2. The PBS setup was used in all cases within the hospital: for 16 patients in the operating theater, 11 in the intensive care unit, 2 in the coronary intensive care unit, 7 in the cath-lab, and 4 in the emergency department. Before the initiation of ECLS support, 2 patients were on intraaortic balloon pump for ischemic cardiomyopathy.

Time from cardiac arrest to initiation of ECLS was extremely variable, and 35 of 40 patients experienced cardiac arrest within the hospital. Among the 18 patients (45%) who survived this early phase of resuscitation, 6 (30%) demonstrated the return of intrinsic cardiac function and were weaned off support with an average ECLS duration of 91 ± 57 hours (range, 20 to 240). Two patients were bridged to transplantation after 82 ± 68 hours (range, 30 to 180), and 9 patients (50%) were transferred to a ventricular assist device (VAD) after 37 ± 26 hours (range, 4 to 90 hours) (Fig 1). Eight patients survived hospital discharge, 4 (50%) of whom had required ECLS for drugs intoxication and were weaned off the emergency support (Fig 2). All patients were in CPC 1.

View larger version (21K): [in this window] [in a new window]   Fig 1. Outcome and extracorporeal life support (ECLS) time in resuscitated cardiac arrest population. (Tx = transplantation; VAD = ventricular assist device.)

View larger version (10K): [in this window] [in a new window]   Fig 2. Overall survival in both populations. (D = day; ECLS = extracorporal life support; M = month.) Surviving patients are indicated at diamond for ECLS and at black square for ECLS continued after day 1.

Five patients presented with early pulmonary hemorrhage and 1 patient experienced pulmonary sepsis.

Twenty-two patients (55%) were withdrawn from ECLS before 24 hours because of severe neurologic injury (n = 15), multiorgan failure (n = 4), or futility (n = 3).

	Comment

Top Abstract Introduction Patients and Methods Results Comment Conclusion Acknowledgments References

 
Current resuscitation attempts from cardiac arrest yield suboptimal results, with survival varying from 1% to 5% for the out-of-hospital cardiac arrests and from 17% to 25% for the in-hospital arrest [1, 2]. Spontaneous circulation is restored in 50% of individuals who receive CPR, among whom 10% to 30% acquire permanent brain damage [12, 13]. The feasibility of emergent cannulation and bypass support for emergencies depends on a collaborative effort between in-house surgical, cardiology, anesthesia, emergency room, nursing, and perfusion personnel [14].

Early reestablishment of hemodynamics during refractory cardiac arrest may facilitate survival by avoiding ischemic neurologic insult while providing essential cardiac and renal perfusion. During cardiac arrest, cerebral oxygen storages are consumed and consciousness is lost within 20 seconds; adenosine triphosphate and glucose disappear in 5 minutes. Restored circulation is followed by global and multifocal cerebral hypoperfusion [13]. Complex chemical disturbance accounts for the death of vulnerable neurons, and encephalopathy develops over a period of 3 days or longer.

After cardiac function was restored, patients underwent serial neurologic evaluations within 12 hours of institution of ECLS that allowed neurologic viability to be established. In most patients, the decision to terminate support or to proceed to long-term mechanical assist was made within 24 hours.

This protocol allowed reasonable initial mechanical circulatory support for all patients. The cost associated with a complete disposable circuit (cannulas, tubing set, pump head, and long-term oxygenator) is approximately $2,800 US. The immediate implantation of a uni-VAD or bi-VAD would have led to unnecessary costs for the patients who would not have survived or been viable transplantation candidates. In addition, straightforward VAD therapy would have induced prolonged critical ischemic time until reperfusion, affecting further viability.

ECLS Indication and Patient Selection
Clinical experience with emergency CPB during prolonged cardiac arrest is limited, and survival rates vary between 0% to 64% [5–11]; the range depends on the small number of patients and selection as well as the experience of the team. However, the most important factor for survival seems to be related to the delay until onset of mechanical circulatory support.

Debate in the literature is ongoing regarding ECLS indication versus CPR duration. In a multi-institutional experience, Hill and colleagues [5] reported that the time from witnessed arrest to ECLS had moderate predictive value for mortality and had not been a major consideration for withholding ECLS if evidence of neurologic function persisted. This contrasts with the experience of Hartz and colleagues [8], who suggested 30 minutes as a cut-off for bypass initiation. In our experience, the average 71 minutes of external cardiac massage before the onset of CPB in surviving patients, Table 3 shows that the effectiveness rather than the duration of CPR has to be considered in the decision process.

ECLS Cannulation
Despite occasional reports on the transthoracic institution of emergency ECLS, the femoral approach is the preferred method of cannulation [18–20]. Access to the vessels through the groin is rapid and easy to accomplish anywhere in the hospital while patient is being resuscitated by closed chest massage. Nevertheless, cannulation-related complications, limb ischemia, and major bleeding, are frequent problems that contribute to the significant morbidity associated with emergency ECLS. Magovern [4] reported that 46% of all patients with femorofemoral cannulation for ECLS needed surgical repair. Schwarz [11] reported 24% of patients needed a surgical procedure either to achieve cannula placement or to correct ischemia or bleeding after successful cannulation.

All these experiences are related to direct percutaneous cannulation in which flow obstruction by the cannula, or mechanical vessel wall trauma during insertion can cause life-threatening limb ischemia accentuated by the intense vasoconstriction that accompanies the low cardiac output. Bleeding complications are related to the unsuccessful attempts, especially in the heparinized patient. To overcome these problems, we have adopted a modified Seldinger technique: surgical exposure of the femoral vessels and puncture of their anterior wall under direct vision. Distal limb perfusion follows the cannulation procedure. Despite this technique, 3 out of 18 surviving patients needed reintervention for groin hemostasis.

ECLS Management
The neurologic state of patients was clinically assessed by waking attempts. In case of postanoxic coma, acute neurologic deterioration, or both, controlled ventilation and ECLS were discontinued when brain death was assessed. In other circumstances in which a prediction of permanent vegetative state was possible and complications such as bleeding and multiorgan failure developed, ECLS termination using "letting die" protocols was considered. Adjunctive predictive evaluations included serial EEG, evoked potentials, and transcranial Doppler evaluations, although in our experience they failed to show a reliable correlation with neurologic outcome.

In recent years, hypothermia treatment using the surface cooling method has been performed successfully with the aim of brain protection in patients with postanoxic encephalopathy. The results of two prospective randomized trials that compared mild hypothermia with normothermia in comatose survivors of out-of-hospital cardiac arrest were published in 2002 [21, 22]. Based on the published evidence to date, official guidelines recommend mild hypothermia as a therapeutic tool in the unconscious adult patients, with return to spontaneous circulation after out-of-hospital cardiac arrest. Such cooling may also be beneficial in ECLS patients suffering from postanoxic encephalopathy. Nagao and colleagues [7] reported an interesting experience in 23 patients admitted after out-of-hospital cardiac arrest for whom the protocol consisted of ECLS combined with the insertion of an intraaortic balloon pump and induction of mild systemic hypothermia. After this encouraging experience, future research should evaluate the usefulness and safety of ECLS to provide both systemic cooling and hemodynamic support in cardiac arrest patients.

Despite the use of heparin-coated circuits and a low dose of heparin, bleeding that needed transfusions remained a major problem. Three (17%) out of 18 survivors required massive transfusions. Although Yamashita and colleagues [23] identified bleeding and consecutive multiorgan failure as one main cause of mortality, 1 of the 3 patients with massive bleedings was a long-term survivor in our population.

Peripheral ECLS configuration with right atrial-to-femoral artery bypass can lead to insufficient left ventricular unloading, left ventricular distension, and blood stagnation. Insufficient unloading of the left heart is therefore an important issue, especially for patients with asystole or ventricular fibrillation in whom this condition can sustain pulmonary congestion and edema that hinders left ventricular recovery. Consequently, it is fundamental to restore left ventricular ejection with inotropic agents even if systemic perfusion is adequately maintained by ECLS. In our series the filling pressures were monitored with a Swan-Ganz catheter or transesophageal echocardiography. Although all precautions were applied, inappropriate unloading of the left heart was a common complication that justified the early bridging to other mechanical cardiac assist systems or, as in the last patient, a percutaneous balloon atrial septostomy. Because of the spectacular pulmonary edema regression and on the basis of other experiences in the literature [24], we strongly recommend this mechanical unloading through percutaneous balloon technologies.

The decision to wean from ECLS, to bridge to other mechanical systems, or to transplant depended on many factors. The underlying pathology leading to a corrective intervention or to a rapid recovery justified this short-term mechanical support, and weaning was legitimate after some days of support. Unknown etiology of the cardiomyopathy or failure to attempt satisfactory unloading of the left heart with persistent pulmonary edema led to the decision to proceed with an early bridge to a ventricular assist device with paracorporeal ventricles or to an urgent heart transplantation if the recovery potential was estimated to be unreasonable.

	Conclusion

Top Abstract Introduction Patients and Methods Results Comment Conclusion Acknowledgments References

 
Our multidisciplinary continuous ECLS experience suggests that patients with hemodynamic collapse that is due to cardiac arrest clearly benefit from this method that leads to rapid restoration of hemodynamic conditions. Furthermore, its easy setup, safe management, and efficiency associated with its low cost compared with other mechanical systems make ECLS an attractive and popular therapeutic technology. In addition, therapeutic hypothermia should improve survival in those patients presenting with cerebral ischemic damage before restoration of circulation.

	Acknowledgments

Top Abstract Introduction Patients and Methods Results Comment Conclusion Acknowledgments References

 
The authors thank those people who collaborated in this multidisciplinary approach to cardiac arrest: operating room and intensive care unit personnel, the perfusionist's team, and Dr Eric Pondaven of the Emergency Care Department.

	References

Top Abstract Introduction Patients and Methods Results Comment Conclusion Acknowledgments References

 

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This Article Abstract Full Text (PDF) 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 Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Massimo Massetti Gerard Babatasi Dimitrios Buklas André Khayat Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Massetti, M. Articles by Khayat, A. Search for Related Content PubMed PubMed Citation Articles by Massetti, M. Articles by Khayat, A. Related Collections Extracorporeal circulation Related Article