Extracorporeal Membrane Oxygenation

Extracorporeal Membrane Oxygenation

RESPIRATORY MEDICINE I 0031-3955/94 $0.00 + .20 EXTRACORPOREAL MEMBRANE OXYGENATION Michael D. Klein, MD, and Grant C. Whittlesey, CCP Extracorpore...

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RESPIRATORY MEDICINE I

0031-3955/94 $0.00 + .20

EXTRACORPOREAL MEMBRANE OXYGENATION Michael D. Klein, MD, and Grant C. Whittlesey, CCP

Extracorporeal membrane oxygenation (ECMO) is essentially cardiopulmonary bypass as practiced in the operating room during open heart surgery. The use of cardiopulmonary support outside the operating room was introduced almost as soon as the devices were available for use during cardiac surgery, but they were limited by the fact that the bubble oxygenators would not sustain perfusion for more than several hours without causing significant damage to blood cells and plasma proteins.35,65 In the 1950s, Clowes and colleagues24 used the first membrane oxygenators in which a semipermeable membrane was used to mechanically separate the gas phase from the blood phase while still allowing diffusion to occur. Kolobow and Bowman62 used a silicone rubber membrane for the same purpose, and the gas exchange properties of silicone rubber made this especially effective. ECMO was first applied in adults with pulmonary failure. Two large series in both the United States and Europe in the 1970s, however, demonstrated the lack of effectiveness of ECMO for adult respiratory distress syndrome (ARDS).44, 117 The survival in patients treated with ECMO (9.5%) was essentially the same as in those patients treated without ECMO (8.3%). Despite this disappointing experience, Robert Bartlett and Alan Gazzaniga in Irvine, California, continued to apply ECMO to newborns with pulmonary and cardiac failure with encouraging results. 9, 10 ECMO had initially been tried in prematures with respiratory distress syndrome as

From the Departments of Clinical ECMO (GCW), Pediatric Surgical Research (GCW), and Pediatric General Surgery (MDK), Children's Hospital of Michigan; and Department of Surgery (MDK, GCW), Wayne State University, Detroit, Michigan

PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 41 • NUMBER 2 • APRlL 1994

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part of the concept of an artificial placenta.88, 104 Although there were encouraging experimental results,46, 61 the clinical results were very disappointing because of the high incidence of intracranial hemorrhage in prematures which was worsened by the fact that they needed to be anticoagulated for ECMO.36,83, 113 In the late 1970s, success with treatment of hyaline membrane disease became so great that ECMO did not seem to have a place given its significant complication rate. There remained, however, a small group of full-term newborns with pulmonary failure to whom Bartlett and Gazzaniga9,10 continued to apply ECMO. Their early results prompted the spread of ECMO in this group of full-term newborn patients with pulmonary failure unresponsive to other means of treatment. The technology of newborn ECMO became standardized through a series of meetings occurring first in Irvine, California, in 1979, and then annually in Ann Arbor, Michigan, beginning in 1983. There are currently more than 100 centers performing ECMO throughout the world who participate in the registry of the Extracorporeal Life Support Organization (University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI48109-0331).

THE CIRCUIT AND CANNULATION

Current standard neonatal ECMO technology is employed. The venous drainage cannula is placed via the right internal jugular vein with its distal tip in the right atrium. The arterial perfusion cannula is placed via the right common carotid artery with its tip in the innominate artery, just at the jUnction with the aortic arch. Blood drains by gravity into a collapsible bladder which rests in an electronic control device sometimes called a venous return monitor (VRM). Blood is then pumped by a roller pump through a silicone membrane oxygenator, a heat exchanger, and, finally, into the arterial cannula. If the bladder collapses because of insufficient venous return, the VRM detects that there is insufficient blood to pump: it automatically turns off the pump and sounds an alarm. Some ECMO centers have thought that ligating the jugular vein could be as dangerous to the brain as carotid artery ligation and have chosen to cannulate the jugular vein distal as well as proximal to improve cerebral venous drainage during ECMO. This cephalad cannula is simply "Y'd" into the venous drainage line. Taylor and Walker101 reported 23 newborns including 16 with distal jugular vein drainage in whom they measured blood flow velocity in the superior sagittal sinus. Occlusion of the distal drainage catheter resulted in significantly reduced blood flow velocity in the superior sagittal sinus, and persistent reduction in superior sagittal sinus blood flow was associated with a higher risk of cerebrovascular injury. Kitagawa and coauthors,55 on the other

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hand, studied primates on ECMO with distal and proximal jugular venous drainage. They found no difference in sagittal sinus, venous, or intracranial pressure when the cephalad or distal cannula was clamped, although there was greater venous return to the ECMO pump when the cannula was open. Many centers have been concerned by the necessity for ligating the carotid artery to perform ECMO. The feasibility of venovenous ECMO was demonstrated early using drainage from the internal jugular vein and perfusion into the femoral vein?' 56 Recently, a double lumen venous cannula has become available commercially (Infant ECMO Catheter, Double Lumen, Venovenous, 14 Fr, 10 cm. Kendall Healthcare Products Co, Mansfield, MA). Using this cannula, it is possible to partially support a patient's pulmonary function with ligation of the jugular vein alone. 6,2s PATIENT MANAGEMENT ON ECMO

Once a patient is on ECMO, the Pao2 is controlled by the rate of blood flow through the ECMO circuit. Using standard venoarterial ECMO, satisfactory blood gases can usually be obtained at flows of 100 to 120 mL/kg/min. Although this is equal to the normal cardiac output, it really bypasses only about 70% of the cardiac output, because the single venous drainage cannula in the atrium cannot capture all of the venous return to the heart from both the superior vena cava (SVC) and the inferior vena cava (IVC). A significant amount of blood still goes through the right ventricle to the lungs. Just as in the native lung, the Paco2 is controlled by the rate of gas flow ventilating the membrane lung. Management of patients on venovenous ECMO differs in several ways from a patient on venoarterial ECMO. One must generally accept lower oxygen saturations and expect the venous oxygen saturation to nearly match the arterial oxygen saturation. Because there is no mechanical pump support of the circulation, more concern must be given to cardiac function and pressors may be required. If poor perfusion persists, conversion to venoarterial ECMO by placement of an arterial cannula may be necessary. There is a tendency for patients on ECMO to develop edema. Active attention to this tendency can improve native lung function and also prevent hypertension. Diuresis can be accomplished with drugs such as furosemide, but ultrafiltration also can be used because it is so easily incorporated into the circuit.47,92 These devices also can be used to treat renal failure should it exist. Patients on ECMO are anticoagulated with heparin to prevent thrombosis of the circuit, with its consequent possible embolic problems in the patient. The activated clotting time (ACT) is determined at the bedside once an hour, and the heparin infusion is adjusted accordingly. Tight control of ACTs, maintaining them between

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180 and 220 seconds to prevent thrombosis without causing hemorrhage is essential. Bleeding is a critical problem in newborn ECMO patients because it is so frequently intracranial and devastating in nature. Other means of preventing hemorrhage also are used. Hemostasis at operative sites must be meticulous; fibrin glue has nearly eliminated neck wound bleeding at the authors' center. Vitamin K and fresh frozen plasma are administered as necessary to maintain a normal, or nearly normal, prothrombin time. Platelet transfusions are given to maintain a platelet count greater than 100,000/mm3.93 In some patients who have had life-threatening hemorrhage and were unable to discontinue ECMO, the authors have discontinued heparin altogether for up to 36 hours with no evidence of thrombosis or embolusY4 One complication of ECMO which is correlated with an increased incidence of intracranial hemorrhage is systolic hypertensionY,91 Although a systolic pressure of 90 mm Hg is not two standard deviations above normal for most newborns, an effort is made to keep the systolic pressure less than 90 mm Hg. Hydralazine is used for the first episode, and if a second episode occurs, captopril is begun for long-term control and nitroglycerine is used acutely. Efforts to maintain the patient's weight near birth weight with diuresis and ultrafiltration are also effective. All patients on ECMO have a cranial ultrasound examination each day. Grade I intracranial hemorrhage ("small caudates"), subependymal cysts, or mild edema is not a contraindication to ECMO or its continuation, but once Grade II or greater hemorrhage, severe edema, or periventricular leukomalacia is identified,l09 ECMO is usually discontinued or not instituted rather than risk almost certain extension of the hemorrhage in these heparinized patients. Ventilator management in the patient on ECMO varies according to the underlying philosophy of lung management. Some ECMO centers, in an attempt to prevent barotrauma and oxygen toxicity, use "rest settings": peak inspiratory pressure (PIP) 20 cm HzD, positive end-expiratory pressure (PEEP) 5 cm H 20, rate 20/min, fractional concentration of inspired oxygen (Fio2 ) 0.25. In patients managed in this fashion, a whiteout of the chest is usually apparent on the radiographs as atelectasis occurs.103 This will usually resolve in 3 to 4 days as lung compliance improves. Other centers, such as the authors', believe that the whiteout and atelectasis are important things to prevent.54 Keszler et al53 demonstrated that PEEP of 12 to 14 cm H 20, when compared with PEEP of 3 to 5 cm H 20, prevents deterioration of pulmonary function during ECMO and results in more rapid lung recovery. The authors use a PIP of 25 and a PEEP of 14 with a rate of 20 and an Fio2 of 0.25. Although only a small proportion of newborns requiring ECMO have hyaline membrane disease, there is evidence of surfactant deficiency in patients requiring ECMO which begins to improve 72 hours prior to weaning. 20, 69 Lotze et aI,68 in a blinded, randomized, controlled

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study, showed that modified bovine lung surfactant given to newborns on ECMO improved pulmonary mechanics, increased surfactant protein A in tracheal fluid, and reduced complications. It did not change time to extubation, duration of oxygen therapy, hospital length of stay, or incidence of bronchopulmonary dysplasia. 68 Administration of surfactant might, therefore, decrease the need for ECMO or shorten the ECMO course. Most infants undergoing ECMO have a decrease in cardiac performance, perhaps because of the decreased filling of the right heart; a few (5%) have an exaggerated decrease in cardiac function termed "cardiac stun." This usually begins in the first 8 hours on ECMO and lasts up to 64 hours. It is more common in newborns with congenital diaphragmatic hernia (CDH) and can recur. Patients experiencing cardiac stun seem to have been more ill before going on ECMO and to have a higher mortality after ECMO.73

WEANING AND DECANNULATION

Many criteria can be used to wean patients from ECMO. 42 If one consistently attempts to tum down the pump flow, one will note that less and less flow is needed to maintain adequate oxygenation. Most patients requiring less than 50 mL/kg/min of ECMO flow can be decannulated and maintained on a ventilator if necessary. When approaching these flows, a "trial off" can be performed on conventional "high" ventilator settings to evaluate the patient's progress. Some centers think that a trial off is a stressful event that can, of itself, induce shunting and therefore prefer to follow the patient's compliance or end tidal CO2 as indicators of recovery of the native lung. Several centers have embarked on reconstruction of the carotid artery following ECMO.1,23, 29, 95 The authors believe that this reconstruction is unwise, because any ischemic damage that may have occurred has already been done during the several days on ECMO, and there is still the possibility of embolic phenomena from the carotid suture line or from intimal damage which the cannula may have caused in areas that cannot be seen from the arteriotomy?7 In addition, stenosis may occur at the anastomosis. 1°O Repairing the carotid artery might be more reasonable if perfusion had been supplied cephalad during ECMO or if there were any evidence of cerebral damage related to ligation of the common carotid artery in these ill newborns. Experience from the literature on adults indicates that restoring flow after acute occlusion of the carotid artery is controversial and may have a place only when there are associated neurologic symptomsY, 14, 75 Although right carotid flow is not restored following ligation without surgical reanastomosis, the left carotid

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flow seems to undergo compensatory increase.67 Duplex Doppler ultrasound examination has demonstrated a decrease in right middle cerebral artery blood flow velocity when the carotid is ligated which returns in 3 to 5 minutes to 70% of baseline, indicating rapid establishment of collateral flow?4 There is also evidence that cerebral blood flow is no different in patients in whom the carotid artery has been anastomosed and those in whom it has been ligated.82 Although the authors do not agree with reconstruction of a previously ligated carotid artery, we do believe that preservation of an intact common carotid artery is something for which we should strive. Our preferred method of cannulation in children without diaphragmatic hernia or cardiac failure who require ECMO for pulmonary support is venovenous ECMO through a double lumen internal jugular vein cannula. Management of the patient with CDH requires some special discussion. Originally, ECMO was used to "rescue patients" after operative repair who developed pulmonary arterial hypertension (PAH) unresponsive to other treatment. It was then used to stabilize children who were thought to be "too ill" to go directly to the operating room, but operative repair was still thought to be urgent and was performed on ECMO.26 The hernia is now thought to be incidental in most cases, with P AH being the life-threatening illness. PAH is treated with or without ECMO, whereas the mass of the hernia is managed by nasogastric decompression and pharmacologic paralysis. IS Timing of operation is then a surgical judgment, taking all factors into consideration, and can often be performed after ECMO decannulation and weaning from high Fio2s and PIPs.

INDICATIONS

In the 1970s and 1980s, there was controversy as to whether ECMO should be performed at all and which patients it might benefit. A National Institutes of Health (NIH) consensus conference, however, has agreed that ECMO is an acceptable, if not an absolutely necessary, part of the modern newborn therapeutic armamentarium. ll5 There are still several newborn centers38, 116 at which physicians believe that they are able to treat the same group of patients usually treated by ECMO, with other means of therapy, primarily "gentle ventilation." Most centers, however, have not been able to duplicate these results and continue to rely on ECMO. This reliance on ECMO as a "final" or "rescue" therapy has not hindered the development of other therapies for the diseases that ECMO is designed to treat. Negative pressure ventilation also has seemed to have some success,94 as have various forms of high frequency

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ventilation. 22,39 Many ECMO centers use high frequency ventilation both jet and oscillatory3o,59, 108 and continue to investigate other options such as nitric oxide and adenosine. ECMO is invasive therapy which carries with it the threat of serious morbidity. Thus, much effort has been expended to define the groups of patients who might be expected to benefit from it. These data are collected in the hope that they can be used to identify patients who could be predicted to need ECMO eventually as well as to eliminate from consideration patients who will not respond to or require ECMO. Several scoring systems have been developed to indicate which patients are, indeed, most at risk of dying and, therefore, most likely to benefit from ECMO.81 Currently, the most useful seems to be the oxygenation index (01 = mean airway pressure X (Fio2 X 100)/Pao2 ).45 This index is the only predictive score for which the same numbers have been reliable at different institutionsY' 17, 37 The oxygenation index (01) is determined on three blood gases, at least 30 minutes apart. Patients with an 01 greater than 25 have a 50% chance of dying, and an 01 greater than 40 predicts an 80% chance of dying without ECMO. In most centers, a newborn who has been on the ventilator for fewer than 7 days and, despite maximal therapy, is unable to maintain a Pao2 over 60 mm Hg for 12 to 24 hours is also considered a candidate for ECMO. Special attention has been turned to scoring systems in CDH, because the belief persists that some of these infants simply do not have enough pulmonary tissue to survive without a ventilator or an ECMO circuit. 21 None of these scoring systems, however, has been reliable enough to keep patients with CDH off ECMO based on a poor prognostic score. 79 Time on a ventilator also seems to predict recovery of lung function. It seems that adults who have been on a ventilator more than 5 days, and children who have been on a ventilator more than 7 days, are unlikely to recover function and wean from ECMO. It was thought that newborns had to be fewer than 7 days old to benefit from ECMO, perhaps because PAH or "shunting" is usually resolved by then, and children with respiratory failure who are older than 7 days old are likely to have substantial pulmonary parenchymal disease. The authors have learned, however, that newborns 10 or even 14 days old can benefit from ECMO, and shunting can continue well into the second week of life. In most centers ECMO has been restricted to newborns weighing more than 2000 g and older than 35 weeks' gestation because of the high incidence of intracranial hemorrhage in premature infants treated by ECMO. Bui et aP9 have estimated that, with proper selection, one might expect a 50% survival rate in this group without a significantly larger morbidity than exists for term infants. More recently, the ECMO center at the National Children's Hospital in Washington, DC, reported a significantly higher risk of both dying and of developmental delay among

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survivors for newborns between 2000 and 2500 g compared with those over 2500 g.86

RESULTS OF ECMO IN THE TREATMENT OF NEWBORNS WITH RESPIRATORY FAILURE Survival

Results with newborn ECMa have been excellent (Table 1). Most centers report a survival of 80% in their group of patients whose mortality they had predicted to be 80% without ECMG. 8 , 27, 98, 107 Why does ECMa seem to work in newborns in the 1990s when it was not effective in adults in the 1970s? The simple reason is that, in newborns, usually a different problem is being treated. The majority of newborns who successfully respond to ECMa do not have serious parenchymal lung disease but, in fact, have primary pulmonary hypertension of the newborn (PPHN), sometimes called persistent fetal circulation (PFC). In PPHN, high pulmonary artery resistance limits blood flow through the lung. This decreased blood flow through the lung results in hypoxemia, hypercapnia, and acidosis which, in tum, further stimulate pulmonary arteriolar vasoconstriction. The increase in pulmonary artery pressure induces a state of right heart failure that can lead to biventricular failure and hypotensi<~n. Blood that cannot flow through the lungs is shunted right to left across the patent foramen ovale and patent ductus arteriosus. PPHN is a response of the lung to an insult. It occurs, most commonly, in meconium aspiration syndrome and CDH, but it can be a feature of hyaline membrane disease, and it can also occur without any known inciting cause. ECMa treats PPHN by first mechanically removing blood from the right side of the circulation, thus decreasing pulmonary artery Table 1. NEONATAL ECMO SUMMARY CUMULATIVE DATA (APRIL 1993) FROM THE ELSO REGISTRY Primary Diagnosis Meconium Aspiration Syndrome Congenital Diaphragmatic Hernia Pneumonia/Sepsis Primary Pulmonary Hypertension of the Newborn Other Total Neonatal ECMO

# Reported

# Survived

Survival Rate

2,895 1,455 1,131 953

2,710 854 868 796

94% 59% 77% 84%

1,233 7,667

1,010 6,238

82% 81%

Data from the Neonatal ECMO Registry of the Extracorporeal Life Support Organization (ELSO), Ann Arbor, Michigan, April 1993.

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pressure. Second, ECMO supplies a drug, namely oxygen, which is a potent pulmonary arteriolar dilator. Third, ECMO treats the blood so that when infused, it will be alkalotic, hypocapnic, and hyperoxic, again causing pulmonary arteriolar vasodilatation as well as preventing endorgan damage. This explanation for ECMO success differs somewhat from the standard view that it provides lung rest and avoids the deleterious effects of barotrauma and oxygen toxicity while preventing endorgan failure, but it does not in any way deny it. Two studies demonstrate that ECMO does not cause improvement in gas exchange so much by an improvement in pulmonary mechanics, as by increased effective capillary blood flow.17, 63

Complications

Complications of ECMO also are reported in the registry data (Table 2), although reports from individual centers frequently give a better idea of the impact of these complications. At Kosair Children's Hospital, Louisville, there were 96 surgical complications in 67 newborn ECMO patients?8 Of 225 newborns, 158 patients (70%) had no complications. In the 67 who experienced complications, bleeding occurred in 37 (16%), initial cannula placement problems in 17 (8%), thrombus formation in 15 (7%), hemothorax, pneumothorax, or effusions in 11 (5%), mechanical problems in 11 (5%), and miscellaneous in 5 (2%). Mortality was significantly higher in patients who had complications, but not in those with mechanical problems, thrombus formation, or catheter-related problems. Table 2. NEONATAL ECMO COMPLICATIONS CUMULATIVE DATA (APRIL 1993) FROM THE ELSO REGISTRY Complication Mechanical Blood Clots in Circuit Cannula Problems Air in Circuit Oxygenator Failure Patient InfarctJlCH Seizures Dialysis or Hemofiltration Hypertension Creatinine >1.5 mg/dL Hemolysis Bleeding at Cannulation Site

# Reported

% of Total

% Survival Rate

1,438 718 406 339

19 9 5 4

76 77 74 64

1,266 1,037 994 816 794 705 523

17 14 13 11 10 9 7

57 66 60 76 59 71 73

Data from the Neonatal ECMO Registry of the Extracorporeal Life Support Organization (ELSO), Ann Arbor, Michigan, April 1993.

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Follow-up

Careful follow-up studies of ECMO patients are now available. As many as 26% will demonstrate some abnormality of physical growth during the first year of life, and approximately one third require rehospitalization in the first year, usually for respiratory illness.89 Approximately 70% of survivors of ECMO have little or no deficit. Twenty percent have a significant problem, and 10% have a severe impairment that is usually neurologicaU' 48,64, 102, 106 These results are similar to those in patients with the same critical illnesses treated without ECMO,16, 25, 41 Advocates of ECMO would be quick to point out, however, that true controls for ECMO patients are difficult to find because without ECMO, 80% of them would have died,

OTHER APPLICATIONS OF ECMO

As the experience with newborn ECMO has increased and its success has become difficult to deny, the technology and experience with the equipment has improved, which has encouraged many investigators to apply ECMO to other areas once again.

Cardiac ECMO

One area where ECMO has been successfully applied is for the support of children with low cardiac output or pulmonary vasoreactive crisis following cardiac surgery,31, 32, 76, 84, 87, 112, 118 It also has been applied in cardiac transplant patients,33, 40 and in the preoperative support of patients with congenital heart disease. 49 These patients are generally not appropriate candidates for forms of cardiac support usually used in adults, such as the intra-aortic balloon pump. This inappropriateness is primarily because their vessels are too small and their cardiac rates too great. In addition, the balloon pump treats left-sided failure, and most children have primarily right-sided failure that becomes left-sided or biventricular only later. ECMO has been applied in this group of children, both with standard neck cannulation used for newborn ECM057 and with traditional transthoracic direct cardiac cannulation as performed in the operating room.51 The management of these patients is considerably different from that of patients on newborn ECMO for pulmonary support. Children who require cardiac support and who have a significant degree of left ventricular failUre will usually require separate decompression of the left side of the heart with a left atrial or left ventricular vent. In addition,

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these patients require very high flows in an attempt to decompress and rest the distended, overworked heart for some period of time, usually 48 to 72 hours, before it can be expected to recover. Such high flows through an oxygenator in a patient with a normal lung can result in high Pao2s, and low Paco2s. Frequently the membrane lung must be ventilated with a reduced Fio2 to avoid hyperoxia, and occasionally, a small amount of CO2 must be added. After open heart surgery, there are far more problems with bleeding than in newborn patients, requiring careful attention to the details of coagulation management. The authors give cardiac ECMO patients a minimum of 10 mL/kg of fresh frozen plasma every 6 hours. This practice, together with the need for frequent platelet and red cell transfusions, makes it appropriate to use ultrafiltration to keep the blood volume low and the heart undistended. When such patients are ready to be weaned, it is necessary to reload them with volume to provide sufficient atrial and ventricular filling for optimal cardiac function. A simple trial off ECMO will usually not suffice. Results in cardiac ECMO have not been as good as with newborn ECMO (Table 3), and survival rates range from 32% to 63%. ECMO for Pulmonary Parenchymal Disease

Interest has revived in the treatment of both adults and children with pulmonary parenchymal disease since the successful clinical trials initiated by Luciano Gattinoni,43 Gattinoni and his coworkers60 applied clinical concepts developed by Kolobow at the NIH. They had found experimentally that oxygen diffused so readily across the alveolar-capillary membrane that ventilation of the lung should not be necessary. They demonstrated that, by holding the lungs expanded with pure oxygen, an adequate Pao2 could be maintained, even in a diseased lung. If adequate oxygenation could be maintained, an extracorporeal system would only need to remove CO2 , The term ECC02R was coined to describe this procedure because CO2 was removed extracorporeally using relatively low blood flows of 20 to 60 mL/kg/min, as opposed to the higher flows required for oxygenation and CO2 removal of 100 to 120 mL/kg/min. Using low-frequency inverse-ratio ventilation with and without extracorporeal CO2 removal in their high risk group of ARDS patients, they demonstrated an overall survival of 79% in a group of patients who had the same entrance criteria as the NIH prospective trial.ll7 The only difference in this group was that they required the static lung compliance to be less than 30 mLI cm H 20. If one looks at only the patients placed on extracorporeal CO2 removal in this study, 50% survived, which is significantly better than the 15% reported in the NIH trial. The work of Gattinoni and the increasing sophistication of the technology available in neonatal

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Table 3. CARDIAC ECMO SUMMARY PRIMARY DIAGNOSIS AND MAJOR COMPLICATIONS CUMULATIVE DATA (APRIL 1993) FROM THE ELSO REGISTRY

Primary Diagnosis Post-Op Cardiac Surgery Post-Op Transplant Other Total Cardiac ECMO

Complications Mechanical Oxygenator Failure Cannula Problems Tubing Rupture Patient Dialysis or Hemofiltration Surgical Site Bleeding Creatinine >1.5, <3.0 mg/dL Other Hemorrhagic Complications

# Reported

# Survived

% Survival Rate

726 40 100

310 13 63

43 32 63

866

386

45

# Reported

% of Total

% Survival Rate

46 47 13

5 5 2

26 30 23

208 203 119 91

24 23 14 11

31 35 22 35

Data from the Neonatal ECMO Registry of the Extracorporeal Life Support Organization (ELSO), Ann Arbor, Michigan, April 1993.

EeMO has caused a resurgence of interest in using EeMO to treat pulmonary parenchymal disease in older children and adultsYo The survival of patients treated in this mannerA' 66. 85 has not been as good as those reported in newborns (Table 4), but they are improving as the applications and limitations of the technology are discovered. 3 Of the first ten adult patients treated at the University of Michigan, four survived. 5 At St. Louis University, 24 patients, 4 months to 16 years old, were treated with venoarterial EeMO for respiratory failure. Eight (33%) were long-term survivors. 111 Although pulmonary parenchymal disease requiring treatment with EeMO is usually classified as ARDS, many specific causes or diagnoses have been reported as responding to EeMO. These include respiratory failure complicating cesarean section,sz pulmonary alveolar proteinosis,72 and bridge to lung transplantation. 34• 50. 96 EeMO has even been applied with success in respiratory failure complicating trauma in which the likelihood of bleeding complications might have been thought to be a contraindication.97 The driving force behind the application of EeMO to pulmonary parenchymal disease is the poor outcome of treating this disease with other means. In 1974, 9.5% of patients meeting entry criteria for the NIH trial survived with EeMO. Throughout the 1980s, most centers reported similar results, continuing to contradict the clinical impression of progress related to improved techniques of ventilation and critical care. In

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Table 4. PEDIATRIC ECMO SUMMARY PRIMARY DIAGNOSIS AND MAJOR COMPLICATIONS CUMULATIVE DATA (APRIL 1993) FROM THE ELSO REGISTRY

Primary Diagnosis Viral Pneumonia Bacterial Pneumonia ARDS Aspiration Other Total Pediatric ECMO

Complications Mechanical Oxygenator Failure Cannula Problems Tubing Rupture Patient Dialysis or Hemofiltration Surgical Site Bleeding Culture Proven Infection Other Hemorrhagic Hemolysis Creatinine> 1.5, <3.0 mg/dL Seizures

# Reported

# Survived

% Survival Rate

156 38 137 53 129

78 18 59 31 60

50 47 43 58 47

513

246

48

# Reported

% of Total

% Survival Rate

95 71 42

19 14 8

35 37 43

146 141 103 68 64 56 55

28 27 20 13 12 11 11

29 39 42 32 34 20 38

Data from the Neonatal ECMO Registry of the Extracorporeal Life Support Organization (ELSO), Ann Arbor, Michigan, April 1993.

1991, Suchyta et al99 reported the first significant improvement to 45% survival, a result which seems to be due to the introduction of rigid protocols for care in anticipation of another controlled trial of ECMO. Results in children with ARDS are similarly poor with mortality rates of 75%.105 Most centers have discovered that patients with pulmonary parenchymal disease frequently need to be on ECMO much longer. Rather than the 5 to 7 days usually required for neonatal ECMO or ECMO for cardiac support, these patients may need to be on ECMO for 2 to 6 weeks. It would seem that one must truly support the patient until the lung itself can heal, whereas in newborn ECMO, one is simply waiting for the pulmonary arteriolar circulation to dilate, allowing proper blood flow to the lung. Bleeding is still a significant complication in adult and pediatric pulmonary ECMO, and frequently the massive transfusions required to replace the blood loss have deleterious effects on the lung?O Cannulation considerations are also different in adult and pediatric pulmonary support. Most adult centers use some form of venovenous ECMO with the groin as the access site. This can be done by cutdown on

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the blood vessels; percutaneous cannulae are also available. This does not provide full pulmonary support but can remove significant CO2 and usually provide enough oxygenation for survival, even if apneic oxygenation is not employed. One must be careful in applying other forms of groin cannulation for ECMO. Standard venoarterial ECMa from the groin may not work. Even if the venous drainage cannula is passed up to the level of the atrium, a short arterial return catheter will not perfuse the aortic arch with oxygenated blood if cardiac output is significant.90 Longer arterial cannulas to reach the aortic arch are not readily available commercially. Mixing and recirculation of blood in venovenous ECMa is also a serious concern. The newborn double lumen cannula has the perfusion holes oriented at right angles so that oxygenated blood from the circuit will be perfused directly across the tricuspid valve to the right ventricle and have less chance of being recirculated into the drainage lumen. Centers doing older patient pulmonary ECMa frequently indicate that it is best to have the venous drainage cannula low, near the renal veins, and to have the tip of the end hold infusion cannula about the level of the diaphragm returning blood to the atrium. ECMa is not the type of procedure that can be put together on the spur of the moment from a few spare parts by any group with experience in extracorporeal circulation such as dialysis, plasmapheresis, or open heart surgery. It requires a cohesive group of people dedicated to the study and practice of extracorporeallife support at a given institution.

SPECULATION

ECMa has been demonstrated to be effective therapy for newborns with pulmonary insufficiency characterized by PAH. It also has demonstrated success in supporting cardiac function following open heart surgery in children. The increasing experience with ECMa in newborns and cardiac patients, along with the improvements in technology, have caused investigators to relook at its application to older children and adults with parenchymal disease. ECMa, or ELS, is likely to become a regular part of critical care in the future. The two major stumbling blocks to the broad acceptance of ECMa, systemic anticoagulation with heparin and ligation of neck vessels serving the brain, are currently being investigated. A prospective, randomized, controlled trial of a heparin-coated oxygenator and circuit has already been carried out in Marburg. 58 Although the hollow fiber oxygenator which was coated had significant plasma leakage, they had fewer bleeding complications and more survivors with the heparin coated circuit. Different heparin coatingsBO and systemic drugs other than heparin18,71

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continue to be investigated in hopes that bleeding and thrombotic complications can be reduced. Some have even suggested that standard ECMO can be performed without heparin for at least short periods of time. ll4 It is entirely likely that very soon ECMO can be performed with percutaneous cannulation not requiring any vessel ligation, using heparin-coated circuits that require little or no systemic anticoagulation. If extracorporeal lung assist (ECLA) could be performed routinely, it would avoid the problems of barotrauma associated with mechanical ventilation, and we might look forward to the day when the mechanical ventilator is placed in the closet, along with the rocking bed and the iron lung.

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