The use of extracorporeal membrane oxygenation (ECMO) for cardiac failure has been increasing over the last decade. Increasingly complex repairs in neonates and infants with complicated congenital cardiac anomalies have lead to this increase in the use of ECMO. The development of implantable and paracorporeal mechanical support devices is underway and clinical applications are being evaluated.1 Use of ECMO in such a high-risk population is associated with a significant morbidity and mortality and also involves substantial resource utilization. ECMO, therefore, forms an integral part of the armamentarium of pediatric cardiac surgeons. Definitive criteria for the initiation of ECMO vary from institution to institution.
We describe our recent experience with this therapeutic modality in a single tertiary care university-associated children's hospital. We have reviewed and published our experience with ECMO previously. We report our results of postcardiotomy ECMO from January 2001 through September 2004. This study describes the patient demographics, clinical variables, technical considerations, and laboratory markers and identifies their relationship with outcomes.
Materials and Methods
A retrospective review of the medical records of all patients with congenital cardiac defects requiring corrective or palliative cardiac surgery that were then supported with ECMO between January 2001 and September 2004 (45 months) was undertaken. Hospital records, operative reports, perfusion data, and pediatric intensive care unit (PICU) records were reviewed to collect demographic information, operative, and postoperative data.
The data were formatted into a structured database and various outcome predictors were tested for an association with survival to hospital discharge. Patient demographics and characteristics such as underlying cardiac lesion, lactate level and pH at initiation of ECMO, presence of ongoing cardiopulmonary resuscitation (CPR), unit of initiation, renal failure on ECMO, requirement of continuous venovenous hemofiltration, and the overall duration of ECMO were analyzed. The effects of these factors on the ability to wean off ECMO for > 24 hours and survival to hospital discharge were studied. Complications occurring on ECMO were noted and their correlation to an adverse outcome was analyzed.
A total of 94 patients were placed on ECMO at our institution during this period. Of these, 84 patients were placed on ECMO after undergoing corrective or palliative cardiac surgery for a congenital cardiac anomaly. Thus, postcardiotomy patients represented 89.4% of the total pediatric patients placed on ECMO during this 45-month period. One patient was placed on ECMO after an orthotopic heart transplant, whereas 83 were placed on ECMO after corrective surgery. Three patients required additional support runs after initial ECMO weaning.
The ECMO circuit used at our institution underwent changes over the study period. The circuit initially consisted of a venous cannula draining via standard PVC tubing to a 35-ml silicone bladder (Medtronic Inc., Minneapolis, MN). Blood was drawn from the bladder across super Tygon tubing used for the raceway by a roller pump (Stockert Instruments/Sorin Biomedical, Irvine, CA) and fed into a 0.8-m2 membrane oxygenator (Avecor-Medtronic Systems, Minneapolis, MN). Blood then proceeded to an ECMOtherm II (Avecor-Medtronic Systems) heat exchanger and then past a standard bridge that was clamped and opened every hour to maintain patency, and finally to the arterial inflow cannula and back to the patient.
In January 2003, the circuit tubing was changed to Trillium tubing (Medtronic Inc.) and the bladder was removed from the circuit and changed to straight 6-inch silicon tubing. The heater was changed to a Myotherm heat exchanger (Medtronic Inc.). The standard bridge was removed and replaced with a bloodless bridge isolated from the arterial and venous limbs of the circuit with high-flow stopcocks. This eliminated the need to clamp and unclamp the bridge every hour. We also changed the way we primed the circuit to allow us to have a sterile loop to hand off to the surgeons rather than trying to add sterile extensions to the individual circuit limbs to hand off to the surgeon.
Heparin is administered at a concentration of 100 units/ml and dose titrated to maintain an activated clotting time of 180 to 200 seconds. In patients requiring ECMO in the operating room, separation from cardiopulmonary bypass (CPB) and reversal of heparin was attempted before reheparinization and initiation of ECMO to improve hemostasis. On institution of ECMO, inotropic support was weaned to minimal levels to keep mean arterial blood pressures at 50 mm Hg. Flow rates of 100 to 200 ml · kg–1 · min–1 were maintained depending on physiology, serum lactate levels, and mixed venous oxygen saturation. Ventilator settings are generally set to “ECMO Resting settings,” which are usually a rate of 10, positive end-expiratory pressure of 10, delta P of 10, and 40% Fio2 and the ECMO sweep flow is used to adjust CO2. Nitric oxide (Inotherapeudics, Clinton, NJ), beginning at 20 to 40 ppm and weaned according to protocol, was used in children with refractory pulmonary hypertension. All patients on mechanical support were given neuromuscular blocking agents and heavily sedated with benzodiazepine and narcotic analgesia.
Separation from ECMO was accomplished by gradual weaning of support flow while increasing inotropic and ventilator support. When flow rates were decreased to approximately 25% of maximal support, the bridge between the arterial and venous systems was opened by turning the stopcocks allowing blood flow though the bridge from arterial to venous side. The arterial and venous limb above the bridge was clamped to isolate the patient from ECMO flow and the circuit was allowed to recirculate. Once the patient was off complete support, hemodynamic stability was monitored and tissue perfusion was assessed by serial arterial blood gases with serum lactate and base deficit values. Cannulas were then removed after approximately 1 hour of hemodynamic stability. All purse string sutures were left in place and resnared. The chest was restented open after cannula removal and a sterile Ioban dressing was reapplied.
Thirty-nine (46.4%) patients were placed on ECMO in the operating room because of an inability to separate from cardiopulmonary bypass. All were cannulated through the chest in the aorta and right atrial appendage and were brought to the PICU with open, stented chests. Those who were off CPB but were hemodynamically critical were brought to the unit with cannulation sutures in place and snared. Forty-five (53.6%) were placed on ECMO in the pediatric intensive care unit, and this was accomplished through the sternotomy incision in 41 (91.1%) while four patients (8.9%) were cannulated via the neck using a percutaneous or cutdown technique.
A Pearson chi-square test or Fisher exact test was used to assess categorical comparisons between groups. Differences between group means for continuous measurements were tested by the Student's t test and checked by the Mann-Whitney test. Values of p < 0.05 were considered statistically significant and all tests were two-tailed. Statistical analyses were performed on a personal computer with the statistical package SPSS 13.0 for Windows (SPSS, Chicago, IL) and R statistical software (www.r-project.org).
The following variables were assessed for associations with survival: age, sex, weight, anatomic diagnosis, presence of significant acidosis, inability to wean from CPB in the operating room, cardiac arrest in the PICU, CPR time, lactate levels at the time of initiation, the presence of renal failure on ECMO (blood urea nitrogen and creatinine levels), requirement for hemofiltration, and duration of ECMO.
A total of 94 children were placed on ECMO at Vanderbilt University Children's Hospital due to cardiovascular failure. Of these, 84 children were placed on ECMO after CHD surgery whereas 10 had nonsurgical causes. Thirty-seven patients underwent two ventricle repairs, whereas 29 patients had hypoplastic left heart syndrome (HLHS) variants and 18 had single ventricle reconstructions without any arch anomalies. The breakdown of the causes for ECMO support depending on etiology is summarized in Table 1. Indications for ECMO support in this study included: 1. Inability to separate from cardiopulmonary bypass in the operating room (n = 39) 2. Hypotension and low cardiac output syndrome on maximal inotropic support in the PICU (n = 12) 3. Pulmonary hypertensive crisis despite maximal medical management with nitric oxide and other pulmonary vasodilators (n = 5) 4. Cardiopulmonary arrest in the PICU requiring CPR (n = 28).
These indications are summarized in Table 2.
The 84 children who were placed on ECMO postcardiotomy were reviewed retrospectively, analyzed, and various outcome predictors were tested for any association with survival to hospital discharge using univariate and multivariate analyses. Median age of the patients was 128 days (range, 1 day to 5 years) and median weight was 4.53 kg (range, 2–18 kg).
Seventy-nine patients were cannulated through their sternotomy incision whereas five patients were accessed through the neck. Cardiopulmonary resuscitation was ongoing in 27 patients at the time of initiation of ECMO, whereas in 55 patients ECMO was initiated under more controlled circumstances. ECMO was initiated in the operating room due to inability to separate from CPB in 39 patients (46.4%), whereas 45 patients (53.6%) were placed on ECMO in the PICU. A total of 52 children (61.9 %) survived > 24 hours after decannulation and 31 patients (36.9 %) survived to discharge. Various predictors affecting the survival to hospital discharge were analyzed using univariate analysis (Table 3).
High arterial serum lactate at the time of ECMO initiation was strongly correlated with nonsurvival (p = 0.004, 95% CI 1.36–6.89). Survival was not correlated with age, weight or gender of the child. Interestingly, CPR at the time of initiation of ECMO did not result in statistically poorer outcome. Nonsurvivors had longer duration on ECMO than survivors (p = 0.003, 95% CI 17.51- 81.17) and the odds of survival dropped significantly after 144 hours (day 6) of ECMO.
There was no statistically significant difference in the survival between the various diagnostic categories listed in Table 1. Of the patients with hypoplastic left ventricle variants, 18 (62.1%) were successfully weaned off ECMO, and of these, 12 (66.7%) survived to discharge. The overall survival in patients with HLHS who required ECMO was 41.4%, whereas those with single-ventricle anomalies without arch obstruction had a survival of 44.4%.
The presence of renal insufficiency on ECMO, as manifested by elevated blood urea nitrogen and serum creatinine levels and the use of continuous hemofiltration, was not associated with ability to wean off ECMO or with survival to discharge. Temporary renal insufficiency on ECMO developed in 41 patients (48.9%).
Significant complications occurred in 67 of the 84 patients placed on ECMO. These are summarized in Table 4. The majority of the complications were related to bleeding at the surgical site or remotely. This was usually managed by repeated beside surgical exploration with correction of coagulopathy along with tight ACT control.
Circuit malfunction with clots in the circuit and oxygenator were found to be the most common mechanical complication and occurred in 19 (23%) of the patients. Circuit replacement was needed in 16 patients, while the oxygenator alone had to be replaced in three patients. Neurologic complications occurred in four patients, of whom three were non survivors. Three patients had intracerebral hemorrhage, and one patient had an ischemic stroke.
The role of ECMO in the support of cardiac patients has been increasing.2 The increasing complexity of congenital cardiac surgery has resulted in the increased use of ECMO support for children after cardiotomy. The ECLS registry for 2004 shows that overall the number of noncardiac ECMO support cases has decreased by almost half.2 The results of our experience with ECMO had been previously studied and published.6 In the intervening time, changes have been made to the ECMO program and circuit. The nature of the underlying lesions, fragility, and immaturity of the neonatal myocardium and associated intrinsic pulmonary vascular disease make this subset of patients extremely susceptible to post-CPB myocardial failure and low cardiac output syndrome. ECMO provides an effective means of mechanical support for these patients and also has a role in the salvage of patients with failing Fontan physiology.10
The initiation of ECMO in the operating room was thought to be an independent factor adversely affecting outcome,8 although this finding has been challenged by other authors.9 In our study, patients coming out of the operating room on ECMO did not have any increased risk of in hospital death.
Prolonged CPR and renal insufficiency had been shown to adversely affect outcome.5,6 To avoid potential cardiopulmonary arrest and CPR, the strategy of coming out of the operating room with the chest stented open and cannulation sutures snared in place was developed for patients with marginal hemodynamics. This facilitates the rapid institution of ECMO in these patients. During the postoperative period in the intensive care unit, hemodynamic and end-organ perfusion status are monitored with parameters such as blood pressure, urine output, serum lactate level, and pH. Worsening of these parameters despite adequate resuscitation with increasing inotropic support is an indication for placing the patient on ECMO. Respiratory failure with pulmonary hypertensive crises refractory to medical management with pulmonary vasodilators also are frequent indications for initiating ECMO support. The ECMO program has available a mobile ECMO circuit, and the team consists of the ECMO technicians, cardiothoracic and pediatric surgeons, pediatric intensivists, and PICU nurses. This facilitates rapid placement on ECMO and potentially minimizes the risk of cardiac arrest.
Longer duration of ECMO has been associated with higher mortality.6,7 In our previous review, ECMO duration of > 72 hours doubled the risk of mortality.6,7 In our current series, patients with ECMO runs < 144 hours (day 6) had a survival of 47%, whereas those longer than 144 hours (day 6) had a survival of less than 5%.
Kolvos et al.3 reported that patients undergoing a two-ventricular repair had better outcomes. For patients undergoing Norwood operations for HLHS, requirement of ECMO was considered to be a separate predictor of mortality.4 In our study, patients undergoing a biventricular repair had a survival to discharge of 29.8%, whereas those with a single ventricular physiology had an overall survival to discharge of 42.5%; 62.1% of patients with HLHS variants were weaned off ECMO. The underlying physiology of the cardiac lesion did not affect the outcome when evaluated by statistical analysis.
Patients with evidence of significant tissue hypoperfusion as manifested by a high serum lactate level had a significantly higher mortality. This indicates that early initiation of ECMO before the development of end-organ damage and multiorgan tissue ischemia would result in better outcomes.
Extracorporeal membrane oxygenation support is an effective mechanical support for cardiopulmonary failure in the postcardiotomy pediatric patient. Early initiation, either in the operating room or in the PICU, before the development of tissue ischemia and end-organ damage will most likely improve outcomes. A committed multidisciplinary team can be developed, and with these resources prolonged ECMO support, previously thought to be a prohibitive risk factor, can also result in successful outcomes. The overall mortality remains high, but ECMO success can be achieved in patients with all kinds of congenital cardiac lesions.
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