663CHAPTER 56 Extracorporeal Life Support TABLE 56 3 Outcomes by Mode and Diagnostic Categories NUMBER (% SURVIVAL) Total Runs Venoarterial Venovenous Survived to DC Neonatal Respiratory 31,591 2917 ([.]
CHAPTER 56 Extracorporeal Life Support resulted in very short life spans for the device and limited their use The development of polymethylpentene membranes that are extremely resistant to plasma leakage and have excellent gas exchange characteristics has made them the preferred device These devices have a low resistance to blood flow and a lower priming volume than the traditional silicone membrane lung, which makes them faster and easier to prime Newer versions maintain excellent gas exchange, have little hemolysis, and have durability for days to weeks without failure In the United States, the Quadrox device (Maquet, Inc.) and the Medos lungs (Fresenius) are currently available Other countries use similar devices These new, low-resistance, hollow-fiber membrane lungs allow easy propulsion of blood from the centrifugal device and are a major reason that centrifugal pumps/hollow-fiber membrane lung devices have become so popular for patients of all ages.45–47,51 A recent evaluation of pumps and oxygenators revealed that, in over 500 patients from 2012 to 2014, centrifugal pumps were used in 67% of patients and polymethylpentene membrane lungs in nearly 100%.40 syndrome, persistent pulmonary artery hypertension of the newborn and sepsis still require ECMO support These infants experience a combination of pulmonary parenchymal and vascular dysfunction that leads to impaired gas exchange The diagnosis and outcome of ECMO applied in neonatal patients are shown in Table 56.4 ECMO provides adequate gas exchange and circulatory support without further exposure to high oxygen concentrations or high airway pressures, thus, fostering healing of the damaged lungs The circulatory changes that result from initiation of ECMO also lower pulmonary vascular resistance Draining right atrial blood reduces right atrial pressure and promotes closure of the foramen ovale In addition, the reduced blood flow to the pulmonary vascular bed decreases pulmonary flow, reduces pulmonary artery pressure, and relieves right-to-left shunting through the patent ductus arteriosus Well-oxygenated blood flowing left to right through the patent ductus arteriosus promotes its closure By relieving hypoxia, hypercapnia, and acidosis, ECMO promotes relaxation of pulmonary vascular tone The amount and extent of pulmonary arteriolar smooth muscle begins to regress These changes allow the transition to a mature circulation The infant continues to receive ECMO until parenchymal lung disease heals sufficiently to allow adequate gas exchange or fetal pulmonary artery flow converts to a mature state and adequate gas exchange occurs However, pulmonary function tests indicate that infants are often weaned from ECMO with only moderate improvement in mechanical lung function These observations support the impression that circulatory abnormalities contribute significantly to neonatal respiratory failure and may partially explain the difference in outcome between neonates and older patients treated with ECMO Historically, neonates have had the best survival of all ECMO groups (.70%) In recent years, as more complex patients with multiple-organ failure have received ECMO, overall survival in neonates has shown some decline Patient Populations Treated With Extracorporeal Life Support Neonatal Cardiopulmonary Failure The majority of ECMO patients reported to the ELSO registry were neonates with respiratory failure (Table 56.3).54,55 The advent of inhaled nitric oxide, surfactant, high-frequency ventilation, and improved pre- and postnatal care has decreased the frequency of ECMO use in these small patients Nonetheless, 800 infants, on average, receive ECMO each year While neonatal respiratory distress syndrome has virtually disappeared, patients with meconium aspiration TABLE Outcomes by Mode and Diagnostic Categories 56.3 NUMBER (% SURVIVAL) Total Runs Venoarterial Venovenous Survived to DC Neonatal Respiratory 31,591 2917 (63) 1124 (77) 23,119 (73) Cardiac 8252 2917 (63) 1124 (77) 3529 (43) ECPR 1864 756 (41) (33) 775 (42) 9487 1196 (53) 1863 (69) 5573 (58) 11,377 3824 (58) 67 (56) 5980 (52) 4361 1945 (43) 36 (52) 1858 (42) Respiratory 19482 1177 (50) 12,395 (61) 11,565 (59) Cardiac 19627 14054 (43) 509 (43) 8381 (42) 6190 4572 (29) 121 (41) 1827 (29) —- —- Pediatric Respiratory Cardiac ECPR Adult ECPR TOTAL 112,231 ECPR, Extracorporeal cardiopulmonary resuscitation Modified from Extracorporeal Life Support Registry, 2019 663 62,607 (55) 664 S E C T I O N V Pediatric Critical Care: Pulmonary TABLE 56.4 Respiratory Extracorporeal Membrane Oxygenation Diagnoses and Outcome From 2014 to 2019 Total Runs Average ECMO Duration Hours (Longest) % Survived CDH 1253 311 (1733) 50 MAS 718 146 (2286) 92 PPHN 679 168 (1154) 73 Diagnosis Neonatal RDS 28 127 (562) 82 118 182 (1155) 50 32 364 (982) 53 130 (282) 88 1065 182 (1558) 69 Viral pneumonia 330 308 (1680) 71 Bacterial pneumonia 198 327 (4286) 70 484 (671) 66 51 239 (1932) 68 Sepsis Pneumonia Air leak syndrome Other Pediatric Pneumocystis Aspiration pneumonia ARDS, postoperative/trauma 21 212 (711) 66 ARDS, nonpostoperative/trauma 238 377 (4013) 65 Acute respiratory failure (non-ARDS) 357 304 (7503) 63 1686 274 (6011) 60 Other ARDS, Acute respiratory distress syndrome; CDH, congenital diaphragmatic hernia; ECMO, extracorporeal membrane oxygenation; MAS, meconium aspiration syndrome; PPHN, persistent pulmonary hypertension of the newborn; RDS, respiratory distress syndrome Modified from Extracorporeal Life Support Registry, 2019 Infants with congenital diaphragmatic hernia comprise a special subgroup of patients treated with ECMO for severe pulmonary hypertension and respiratory failure Severe pulmonary hypertension or lung hypoplasia leads to about 50% mortality even with ECMO support Morphologic examination, better understanding of the pathophysiology of this lesion, and stabilization with ECMO as needed preoperatively or perioperatively has improved the survival rate in some centers in this challenging group of patients A 2009 study using Congenital Diaphragmatic Hernia (CDH) Study Group data showed that compared with repair on ECMO (44% survival), repair after ECMO showed a survival advantage (77% survival) The decision to repair on ECMO versus after the completion of ECMO is typically a choice by physician, institution, and ECMO team and subject to institutional bias.56–59 Pediatric Patients Approximately 600 nonneonatal pediatric patients are reported to the ELSO registry each year for severe respiratory failure, with an overall survival rate of 53% (see Table 56.3) While pulmonary dysfunction resulting from bacterial or viral pneumonia, aspiration syndromes, intrapulmonary hemorrhage, and acute respiratory distress syndrome (ARDS) formed the majority of ECMO cases in the past, recent years have seen a large rise in less welldefined disorders recorded in the ELSO registry as “other.” This category may consist of patients with sickle cell disease, sepsis, and other diseases.60–63 The enormously heterogeneous older pediatric population spans nearly decades of physiologic development, and cardiorespiratory failure develops as a result of a multitude of different disorders Furthermore, many patients have varying degrees of multiple-organ failure along with respiratory disease at the time that ECMO is instituted Resolution of both lung disease and secondary organ dysfunction must occur to achieve survival These factors result in lower survival rates in older patients treated with ECMO than that achieved with the neonatal patient population One small subgroup of ECLS patients with excellent survival is individuals with status asthmaticus One study of 64 asthmatic patients supported by ECLS noted that the mean duration of ECMO was 94 hours, and 94% of the patients survived VV support was the cannulation mode in 86% of patients.64 One common theme in pediatric ECMO over the past few years is the increasing complexity of patients The multiple exclusion criteria used in the early days of ECMO have now been essentially eliminated, and each potential patient is generally considered on a case-by-case basis Even patients with known bleeding disorders such as hemophilia have successfully received ECMO support.65 Between 1993 and 2007, the percentage of pediatric patients with comorbidities prior to ECMO increased from 18% to 47%.66 Overall, 40% to 50% survived to hospital discharge Patients with pertussis and fungal pneumonia had the highest mortality; these groups remain among the most challenging ECMO patients CHAPTER 56 Extracorporeal Life Support Of interest, pertussis is an exclusion diagnosis in some parts of Europe owing to the poor outcomes with ECMO In some areas of the United States, however, pertussis ECMO patients have been treated successfully One review of 200 pertussis patients who received ECMO found 28% survival, with leukocytosis (and leukoreduction) and pulmonary hypertension associated with poor outcome.67 Variability in strain of pertussis or response to infection may seem to be logical explanations for geographic variability in survival, but this has not been proven Trauma Patients Trauma patients, particularly those with multiple injuries, are at risk of respiratory failure Trauma remains the leading cause of death in young adults Common pathophysiologic mechanisms include direct chest injury-causing pulmonary contusion, long bone or pelvic fractures causing fat embolization, or an inflammatorymediated event following systemic injury ECMO provides “lung rest” by permitting reduced ventilator settings and limiting further ventilator-associated lung injury while maintaining tissue perfusion and oxygenation Trauma patients have been previously excluded for consideration owing to their inherent highrisk bleeding However, many centers have documented success in this patient population In a study comprising 28 adult patients treated with ECMO because of trauma-related respiratory failure, 20 patients were successfully weaned off ECMO and discharged Eight patients died as a result of overwhelming sepsis and irreversible cardiogenic shock Good outcomes in pediatric patients undergoing ECMO following trauma also have been reported, including patients with severe thoracic trauma.62,63 Traditionally, traumatic brain injury (TBI) patients were considered a relative contraindication to ECMO However, more centers are describing successful use of ECMO in patients with TBI, even with recent ICH or with intracranial pressure monitoring in place.68 Craniotomy on ECMO for high intracranial pressure has also been described and, in a 10-year review from the ELSO registry, nonTBI children who underwent craniotomy on ECMO support were described Two survived with minimal neurologic deficits Other trauma-related applications of ECMO include management of patients with extreme hypothermia who require gradual extracorporeal rewarming The old adage that “you aren’t dead until you are warm and dead” in hypothermic arrest holds true—bypass techniques such as ECMO are now considered the standard of care in severe hypothermic arrest resuscitation Multiple “miracle” stories of survival with good neurologic function exist based on ECMO support in hypothermia Trauma patients with massive hemorrhage and ongoing coagulopathy from transfusion-related hypothermia also have received short-term extracorporeal support with bypass to facilitate rewarming to temperatures that help normalize the coagulation process Once rewarming is achieved, cannulas are withdrawn Extracorporeal Membrane Oxygenation and High-Risk Diseases Patients with underlying malignancy form an increasingly large percentage of ECMO support, rising from 0.3% to 1% of pediatric ECMO cases in the most recent review Of 171 patients analyzed from 2008 to 2012, 55.0% survived their ECLS run and 48.0% of patients survived to hospital discharge Recent anecdotal reports have noted that patients with newly discovered malignancy have also received successful induction therapy while on ECMO support.69–71 665 The most discouraging group of patients who have received ECMO are those with underlying bone marrow transplants.72 Although ECLS has been applied to such children, none have been reported as survivors to discharge in the ELSO registry However, anecdotal reports of sporadic survival—combined with pleas from oncologists that the rapid rise of stem cell transplants and today’s conditioning and posttransplant regimens are less toxic, lead to rapid engraftment, and result in cure if the patient can be supported until engraftment occurs—result in application of ECMO in some patients.73 Most patients receive ECMO for respiratory failure (often of unknown etiology) or sepsis The effect of high-risk diagnoses on outcomes with ECMO support is highlighted by the recent evaluation of such patients via the Pediatric Health Information System High risk was defined as diagnoses of bone marrow transplant, leukemia, lymphoma, neutropenia, immune system abnormalities, genetic abnormalities, neoplastic disorders, and complex congenital heart disease (CHD) Bone marrow transplant (81% mortality; OR, 3.49), leukemia (66% mortality; OR 1.88), and neutropenia (58% mortality; OR, 1.62) were associated with higher odds of mortality compared with other pediatric ECMO patients Complex CHD (52% mortality) and genetic syndromes (48%) had no association with outcomes.74,75 New therapies, such as chimeric antigen receptor (CAR) T-cell replacement for malignancy and likely soon for nonmalignant conditions in the future, are often associated with severe systemic inflammatory responses that are short-lived Use of ECMO in such patients has provided support until this phase of treatment response is over Poisonings ECMO has also provided respiratory and/or cardiac support for patients who have ingested toxic substances or overdosed Calcium channel blockers, tricyclic antidepressants, b-blockers, aluminum phosphate, and a variety of other medications have all been successfully treated with ECMO Use of ECMO should be related to the probability that temporary support can allow return of organ function and not necessarily related to clinical presentation, as some of these patients will have manifestations of fixed and dilated pupils, profound cardiac dysfunction to the point of asystole, and features that may seem incompatible with life but, in reality, are consistent with drug toxicity An animal study of resuscitation with ECMO versus conventional therapy in severe carbon monoxide poisoning also found improved survival with ECMO rescue.76–79 Bridge to Lung Transplant One special patient population that is most applicable to adults but also to adolescents and even to younger patients is the use of ECMO as a bridge to transplant With the advent of new equipment and patient management techniques that allow patients to be awake, mobile, and undergo active rehabilitation while on ECMO support, this area represents a new growth region for which excellent results are being reported in both pre- and posttransplant care Especially in patients with severe hypercarbia, such as chronic obstructive pulmonary disease or cystic fibrosis, ECMO can provide an improved quality of life until transplant occurs The artificial lung is also coming closer to clinical reality and may also offer support.80–82 666 S E C T I O N V Pediatric Critical Care: Pulmonary Why Use Extracorporeal Membrane Oxygenation? ECMO avoids the circulatory derangements that often result from extreme forms of mechanical ventilation and provides systemic perfusion without the need for high-dose levels of inotropic agents Thus, ECMO may prevent secondary organ dysfunction While it is desirable to apply ECMO before multiple-organ failure has occurred, many patients already have secondary organ damage prior to ECMO While survival in such patients is less than with single-organ failure, success can be obtained In addition to providing Do2 and circulatory support, ECMO provides a platform to which other organ support devices can be integrated Renal replacement therapy, plasma exchange, and a variety of new filters that may absorb cytokines or provide hepatic support are able to be added as adjuncts to the ECMO circuit without adversely affecting the patient’s hemodynamics.83,84 Extracorporeal Membrane Oxygenation for Cardiac Dysfunction Details on extracorporeal support in cardiac patients are discussed in Chapter 28 Extracorporeal Membrane Oxygenation for Resuscitation Another growing area of the use of ECLS is in support of patients with refractory cardiac arrest.83–93 This type of support is termed extracorporeal cardiopulmonary resuscitation (ECPR), or ECMO during cardiac arrest Many centers maintain an ECMO circuit setup that is preprimed with a crystalloid solution and stored (usually up to 30 days) This is done to facilitate expedient access to ECMO support for ECPR in situations of acute deterioration or whenever there is insufficient time or personnel for routine ECMO Other centers use a portable centrifugal bypass perfusion system that also is easily set up within 10 minutes Both methods use a hollow-fiber membrane lung.85–98 An addendum to the ELSO registry that has been specifically designed for patients experiencing cardiac arrest may provide more detailed information to answer ongoing questions Several adult reports, which may have applicability to larger pediatric patients, have found that percutaneous femoral artery and vein cannulation during arrest is efficient and associated with good outcomes.95–98 Resuscitation efforts even in the field are now also being evaluated, with center ECMO teams or emergency medical personnel placing cannulas and initiating ECMO on-site This process is aimed predominantly at those experiencing acute heart failure with ventricular fibrillation; whether this will result in improved outcomes is yet unknown How these efforts may expand to children is unclear Extracorporeal Membrane Oxygenation and Septic Shock The role of ECMO in severe septic shock is debatable and results vary Patients with cardiomyopathy and vasoconstrictive shock induced by sepsis (so-called cold shock) fare better than those with vasoplegia (warm shock) The most recent international guidelines for the management of septic shock in children specify a grade recommendation for ECMO as a therapy of last resort for refractory septic shock An international retrospective cohort study using data of children admitted to the intensive care unit (ICU) with a diagnosis of severe septic shock between 2006 and 2014 showed survival benefit in pediatric patients treated with ECMO for septic shock Of the 164 patients who met the criteria for severe septic shock, survival to discharge was 40% in the conventional therapy group versus 50% in the ECMO group In children who experienced an in-hospital cardiac arrest, survival to hospital discharge was 18% with conventional therapy versus 42% with VA ECMO This article also reviewed primary outcome by level of mechanical support; survival was significantly higher in patients who received high ECMO flows (.150 mL/kg per minute hours after institution of support) compared with children that received standard ECMO flows or no ECMO flow (82% vs 48% and 42%, respectively) Patients with central cannulation had higher flow rates and improved survival when compared with those with peripheral cannulation.99 Patient Selection Criteria Various mortality prediction criteria have been put forth as indicators of when ECMO rescue is best applied Many of these criteria have been derived from small series of historical data for patients with respiratory failure or were extrapolated from neonatal respiratory failure data Attempts to provide universally accepted criteria for the institution of ECMO have proved to be difficult New severity scores and outcome predictors for ECMO have been developed, although none is perfect The respiratory ECMO survival prediction score, the predicting death for severe acute respiratory distress syndrome on VV-ECMO score, the pediatric pulmonary rescue with ECMO prediction score, the pediatric ECMO prediction score, and the pediatric risk estimate score for children using extracorporeal respiratory support all have some potential, but further refinement is needed (Table 56.5) They are most useful to provide families and clinicians with some general outcome prediction and not for use in individual patient ECMO selection currently Online calculators are available for some of these scores and can be accessed via the ELSO website or from web addresses within the specific publications.100–103 The current state is that almost every patient who receives ECLS is selected on a case-by-case basis The clinical team discusses the risks and benefits of ECLS in light of the current ICU status and makes a decision to either offer ECMO to the family as an option or not Given the complexity of patients receiving ECLS and comorbidities often present, clinicians from other services outside the ICU staff (pulmonary, oncology, neurology, and others) are beneficial in this discussion Many centers also have smaller teams with special expertise or interest in ECLS within the overall ICU faculty who function to provide advice on candidacy, ECLS strategy, and patient management For the majority of patients who undergo ECMO, less invasive methods of respiratory support have failed Such methods of support often include conventional mechanical ventilation in pressure control or pressure-regulated volume control modes, high positive end-expiratory pressure (PEEP), high-frequency ventilation, surfactant, inhaled nitric oxide, prone positioning, and neuromuscular blockade.98–105 While severity scores such as partial pressure of arterial oxygen/ fraction of inspired oxygen (Pao2/Fio2), shunt fraction, compliance and others have been used to identify potential ECMO candidates, the oxygenation index (OI) has remained in favor in children, as it combines the level of ventilatory support being given and the oxygen level obtained in arterial blood It is calculated as follows: OI Mean Airway Pressure (cm H O) FiO PaO (torr) CHAPTER 56 Extracorporeal Life Support 667 TABLE Prediction Scores for Extracorporeal Membrane Oxygenation 56.5 No Variables Core Population PIPER Neonatal respiratory failure Neo-RESCUERS Neonatal respiratory failure Ped-Rescuers Model ROC Development Dataset External Validation Website Reference 0.74 (continuous); 0.73 (binned) 2000–2010 No https://www.elso.org/ Resources/PIPERScore aspx 174 10 0.78 2008–2013 No http://www.neo-rescuers.com 175 Pediatric respiratory failure 13 0.69 2009–2014 No http://www.ped-rescuers.com 176 P-PREP Pediatric respiratory failure 0.69 2001–2013 Yes http://www.picuscientist.org/ pprep 177 RESP Adult respiratory failure 12 0.74 2000–2012 Yes http://www.respscore.com 178 PEP Neo and Peds ECMO All categories 0.75 2012–2014 No; pending https://www.cpccrn.org/ calculators/ecmoprediction/ 179 SAVE Adult cardiogenic shock 11 0.68 2003–2013 Yes https://www.elso.org/ SaveScore/Index.html 180 CDH Pre-ECMO Neonates with congenital diaphragmatic hernia 12 0.65 22 0.73 2000–2015 No CDH On-ECMO https://www.choc.org/ ecmocalc/ 181 CDH, congenital diaphragmatic hernia; ECMO, extracorporeal membrane oxygenation; NeoRESCUERS, Neonatal Risk Estimation Score in Children Using Extracorporeal Respiratory Support; P-Prep, Pediatric Pulmonary Rescue with ECMO Prediction; PEP, Pediatric ECMO Prediction; PIPER, Pittsburgh Index for Pre‚ ECMO Risk; RESP, Respiratory ECMO Survival Prediction; ROC, receiver operating curve; SAVE, Survival After Venoarterial ECMO Scores of greater than 40 or from 30 to 40 without improvement have been associated with high mortality in the past and had been used as ECMO candidacy alerts Recent data, however, have noted doubling of mortality from less than 20% to more than 40% when the OI exceeds 16 In an evaluation of 65 children with serial OI measurements obtained from the electronic medical record from a single center, mortality tripled when the OI exceeded 17.106 In another review of factors associated with death in children with severe respiratory failure, the peak OI and pediatric risk of mortality score were found to be independent predictors of outcome, although no definitive OI cutoff that predicted death could be identified These findings, along with the increased ease of applying ECMO, have led to discussion as to whether ECMO should be applied at OI severity scores much lower than in the past Indeed, in the adult population, there is now discussion as to whether ECMO should be implemented to avert intubation or if it should be performed shortly after the need for mechanical ventilation.107,108 Alveolar dead space has also been linked to outcome, with one study noting that dead space of 30% or greater at the onset of pediatric ARDS differentiated survivors from nonsurvivors The impact of dead space was not significant after 24 hours.109 In an attempt to provide standard definitions for respiratory failure in children and develop consensus regarding pediatric respiratory care guidelines, an expert panel of 19 international clinicians met and examined thousands of published reports by the Rand/University of California, Los Angeles (UCLA) method and achieved consensus results using the modified Delphi method ECLS was one of the nine areas selected for recommendations As there were few high-quality report scores for ECMO as scored by the Rand/UCLA method, recommendations were developed primarily by consensus expert opinion These included the following: Serial measurements of severity of illness as criteria for ECMO should be used rather than a single cut-off value Cases should be discussed among treating clinicians as a team ECMO should not be offered to patients in whom life-sustaining measures were restricted Quality of life and long-term outcomes from comorbidities should also be evaluated All centers should report patients and outcome to a registry such as ELSO Benchmarking of centers against overall data from such registries is useful to improve quality care This consensus report represents the baseline agreement on respiratory definitions and care practices It is likely that further refinement of recommendations will occur over time.110 Physiology of Extracorporeal Life Support: Gas Exchange and Oxygen Delivery Oxygenation The difference between the partial pressure of oxygen (Po2) in the gas supplied to the oxygenator and that in the patient’s systemic venous blood provides the “driving pressure” across the membrane lung As an example, 30% oxygen blended into the gas entering the oxygenator will result in an estimated Pao2 of about 228 torr at sea level The Po2 of venous blood entering the oxygenator depends on the difference between Do2 and consumption in the patient but is about 40 torr in normal conditions Thus, the ... understanding of the pathophysiology of this lesion, and stabilization with ECMO as needed preoperatively or perioperatively has improved the survival rate in some centers in this challenging group of patients... cannulas and initiating ECMO on-site This process is aimed predominantly at those experiencing acute heart failure with ventricular fibrillation; whether this will result in improved outcomes... oncology, neurology, and others) are beneficial in this discussion Many centers also have smaller teams with special expertise or interest in ECLS within the overall ICU faculty who function to provide