673CHAPTER 56 Extracorporeal Life Support Ventilator Management The optimal ventilatory management for patients undergoing ECMO is not known; each center may have its own preference for how to treat t[.]
CHAPTER 56 Extracorporeal Life Support Ventilator Management The optimal ventilatory management for patients undergoing ECMO is not known; each center may have its own preference for how to treat the lungs during ECMO.133–135 Minimizing further ventilator-associated lung injury or oxygen toxicity and providing an environment that promotes lung healing are basic goals For neonatal patients undergoing VA ECMO, most centers use ventilator settings with low peak inspiratory pressure (PIP; ,25 cm H2O), PEEP (5–14 cm H2O), intermittent mandatory ventilation rate (6–12 breaths/min), and Fio2 (0.21–0.30) Lung volume may decrease with such settings in most patients undergoing ECMO and result in generalized opacification on the chest radiograph Maintaining lung expansion and functional residual capacity with higher levels of PEEP (10–15 cm H2O) was associated with shorter ECMO durations in one neonatal study and was recently confirmed in a large adult sample.133,136 A recent evaluation from the ELSO database found the most common settings in children to be a rate of 10 beats per minute, PIP 15 to 20 cm H2O, PEEP 10 to 12 cm H2O, and Fio2 0.40 Driving pressure is also currently a potentially important variable, with suggestions in adults that maintaining this value at less than 15 cm H2O may improve outcomes A new multicenter study of ventilator parameters in adults noted that no specific marker was associated with outcome, although most centers seem to have reduced tidal volumes and reduced driving pressures.137 Both increased tidal volumes and lower driving pressures, likely a representation of improved compliance, were associated with outcomes across the ECMO course.137 The newest concept of mechanical power applied to the lung as the cause of injury is intriguing, yet which component of the power equation is most injurious is not proven.138 Mechanical power is calculated by: Powerrs ⎪⎧ 0.098 i RR i ⎨Δ V i ⎩⎪ ⎡1 ⎢ i EL rs ⎢⎣ RR i (1 I : E) 60 i I: E ⎤ i R aw ⎥ ⎥⎦ ⎪⎫ Δ V i PEEP ⎬ ⎭⎪ The reader is directed to the excellent article on the future of mechanical ventilation by Gattinoni for a more detailed explanation.138 Spontaneous breathing and even removal of the endotracheal tube or early bedside tracheostomy are gaining popularity as clinicians become more comfortable with allowing their patients on ECMO to be awake and alert This facilitates activity and ambulation and is often used for patients bridging to lung transplantation Proponents of spontaneous breathing point out that the natural course of healing in ARDS is about weeks, and that, during the fibroproliferative phase, unmeasurable tidal volumes can be present for days to weeks Thus, trying to “open” these consolidated lungs with recruitment maneuvers or other means may create more harm than merely letting patients recover lung expansion on their own While spontaneous breathing is a good goal, it may result in excessive changes in intrathoracic pressure that may interrupt venous return and may exacerbate or result in ventilator-associated lung injury Adult data indicate that while patients with chronic obstructive pulmonary disease or bridge to lung transplant often well with spontaneous breathing, patients with severely consolidated lungs generally not tolerate spontaneous breathing early in the course As spontaneous breathing efforts in some patients have exacerbated or initiated air leak syndromes, maintaining heavy sedation or neuromuscular blockade may be required until air leaks heal Healing of ruptured alveoli generally occurs within 48 to 72 hours An enlarging pneumothorax that is adversely affecting ECMO support or hemodynamics will require drainage Small pigtail devices are 673 usually adequate, but larger bore tubes are sometimes required Inadvertent puncture of intercostal vessels or the lung itself can be a major source of bleeding; this can necessitate thoracotomy and multiple blood product administration and is associated with reduced survival In patients with severe lung disease, manipulating ventilator settings has little effect on gas exchange Flexible bronchoscopy is useful in patients with excessive secretions or to monitor for infection While concerns for bleeding are legitimate, few complications have been reported when bronchoscopy is performed by experienced providers CT can also be useful to identify and delineate lung pathology In patients who show no signs of improvement over many weeks or are being considered for removal from ECMO for futility, lung biopsy may prove useful, although uncommon.139,140 While inherent risks from bleeding exist with biopsy, results can be useful in identifying diagnoses incompatible with life (e.g., alveolar capillary dysplasia, profound pulmonary fibrosis) or unusual infections not identified by other means Oxygenation and CO2 elimination depend on the function of the ECMO circuit With VV cannulation, less overall bypass is obtained, and the systemic oxygenation provided by ECLS is less than with VA access Arterial oxygen saturations are thus lower with VV support While most patients well with saturations in the 75% to 85% range, monitoring of adequate Do2 by following lactate, venous saturation, urine output, metabolic acid-base balance, and mental status is recommended with these patients As the lungs heal, compliance and tidal volume increase Radiographs of the lung fields gradually improve from atelectatic opacification to increasing lung aeration Increasing oxygenation and concentration of expired CO2 also heralds improved alveolar/ capillary gas exchange Evidence of decreasing pulmonary artery pressure (indicated by resolution of right-to-left intracardiac shunting or other echocardiographic information) in VA support may also signal that the patient is ready to be weaned from ECMO A constant theme in ECMO care today is to be patient and allow lung recovery (and secondary organ failure if present) to occur The duration of ECMO, practiced at a maximum of weeks early in the history of its implementation due to complications that arose, is now much longer; successful survival without the need for transplant has been achieved as far out as over year of support New data demonstrating that lung remodeling or regeneration can occur even up to adulthood are driving clinicians to maintain ECMO or related support for long periods of time In children, whose benefit from lung transplantation may still result in a short life span (10 years or so), these issues are even more complex Today, there are few specific indicators that can identify who will improve with ECMO support; most patients receive ECMO until a life-ending complication occurs, families request withdrawal, or resource use cannot be maintained Sedation and Analgesia Maintaining patient comfort during ECMO can be a challenge, especially during prolonged ECMO runs Sedation and analgesia are provided by routine medications such as morphine, fentanyl, midazolam, lorazepam, among others The ECMO circuit and membrane lung are known to absorb medications, although the extent of changes with the newer systems in use today is unclear.141–143 Drug dependence and withdrawal symptoms become major adverse events and prolong hospital stays for many ECMO survivors a2-Agonists such as dexmedetomidine may be useful to 674 S E C T I O N V Pediatric Critical Care: Pulmonary decrease narcotic or benzodiazepine requirements Multiple reports on the success of maintaining ECMO patients in an awake state have started a new era of ECMO care Patient management now promotes maintaining ECMO patients awake, alert, and even mobile to maintain muscle strength and tone Rehabilitation while on ECMO is especially needed for patients who are bridging to lung or heart transplant Nursing and family support play a major role in the success of providing ECMO with little sedation Weaning From Extracorporeal Membrane Oxygenation A patient can be weaned from ECMO in several ways The most common VA mode weaning involves reducing the ECMO flow rate in set increments every to hours provided that arterial and mixed venous oxygen saturations and gas exchange remain adequate Once ECMO flow is reduced to provide only about two-thirds of cardiac output, ventilator support is increased to levels that are still lung protective Infants are usually considered ready to be trialed off ECMO when flows reach 50 mL/kg or an estimated 10% of cardiac output in larger patients If the patient remains physiologically stable with acceptable blood gas tensions at low flow, the ECMO cannulas are clamped, and the patient is observed while off ECMO support for a short time Some clinicians will not clamp off ECMO; instead, they either rely on the fact that hemodynamics are suitable at low flow or wean flow to the extent that arterial backflow from the patient to the centrifugal pump is occurring (idling flow) Clamping carries risk of cannula clotting if blood is static for too long; most clinicians will reopen (or “flash”) the cannulas every 10 minutes or so to prevent clot formation Idling flow in the centrifugal circuit exposes blood trapped in the centrifugal head to hemolysis If gas exchange and circulation remain stable during the trial, the cannulas are removed and conventional therapy is resumed Quicker weaning methods involve decreasing ECMO flow in larger increments over shorter periods, similar to the way that it is performed during cardiopulmonary bypass in the operating room For VV patients with respiratory failure, Fio2 to the membrane lung and sweep gas should be decreased to the point at which the oxygenator is capped off to ensure that the native lungs can provide adequate oxygenation and ventilation While some clinicians also reduce ECMO pump flow during VV weaning, it is not necessary to wean flow excessively or clamp the patient off ECMO since blood flow is already following the native circulation and the heart is providing the pumping to the body If flow is decreased, it should be maintained at levels not likely to contribute to risk of circuit thrombosis Of note, in patients with severe lung injury, the ability to recover oxygenation may occur prior to the ability to exchange adequate CO2 through the lung Hypercapnia is often the limiting factor in weaning off ECMO in these patients; more time for lung healing must be allotted Newer devices require low blood flows to remove CO2 Transitioning the patient to such devices may allow for the use of smaller cannulas, increase mobility, and provide another support until lung recovery occurs Decannulation Decannulation involves removal of surgically placed cannulas and repair of the operative site, with or without vessel repair Vessels used in traditional, open venotomy or arteriotomy ECMO often can be repaired at decannulation, although this approach is not used universally While it is unclear whether avoiding ligation or repairing cannulated vessels results in long-term improvement in blood flow or reduced risk of stroke from thrombosis or infarct, initial followup of carotid artery repair appears to be beneficial in literature reviews The longest follow-up study of repaired carotid vessels found restenosis or occlusion in 24% Patients with reconstructed vessels had fewer neuroradiologic abnormalities and a lower incidence of cerebral palsy than did unrepaired historical control subjects, although these data represent a small, single-center report and are not the result of a randomized study.144 Femoral vessels are sometimes accessed via a Gore-Tex graft or one made of a similar material sewn into the side of the vessel This graft is tied off at decannulation Vessels accessed percutaneously are not usually ligated either at initiation or decannulation from ECMO Percutaneously placed cannulas are merely withdrawn at decannulation while pressure is applied to the site until hemostasis is obtained Femoral artery repair often is performed to ensure the continued integrity of the vessel and limb perfusion New devices to provide closure of the femoral artery access site without surgical repair may also be advantageous in larger patients Heparin is discontinued at decannulation Normalization of coagulation usually occurs within a few hours Protamine is rarely used for the reversal of heparin-induced anticoagulation at decannulation Venous thrombosis may develop after ECLS has been discontinued, especially with femoral cannulation, which may be an additional reason why heparinization should not be reversed Many clinicians favor some form of anticoagulation or antiplatelet medication following decannulation, especially in adolescent and adult patients When to Stop Extracorporeal Membrane Oxygenation Support As ECMO duration has increased, the decision to withdraw support has remained an individualized one that considers the underlying diagnosis, extent of organ dysfunction, complications, and perhaps further diagnostic tests to establish irreversibility (e.g., biopsy) Valid reasons to withdraw support include the development of complications that are incompatible with long-term survival, such as devastating neurologic events or when the patient is ineligible for transplantation and will not recover (e.g., alveolar capillary dysplasia) Withdrawal of care proceeds in the usual way following extensive family discussion, appropriate planning, and the administration of adequate anxiolysis and analgesia When ready, pump flow can be ceased, and the cannulas clamped, capped off, or removed Some families may choose to cease ECMO but not other means of support, such as vasoactive agents or mechanical ventilation Religious and ethnic practices may also require special considerations when discussing support withdrawal While ECPR initiation has become routine in many centers, the questions of when not to offer ECMO and when to discontinue ECMO efforts if recovery seems futile have opened a new area of ethical discussion Setting goals for support and establishing decision-making processes that are explained to the family prior to initiation of ECMO and during repeated conversations may alleviate some of these situations Complications From Extracorporeal Membrane Oxygenation Complications that occur during ECMO can be mechanical or related to the particular patient The most common adverse events reported to the ELSO Registry are shown in Table 56.7 CHAPTER 56 Extracorporeal Life Support 675 TABLE Common Extracorporeal Membrane Oxygenation Complications and Outcomes 56.7 Complications on ECMO Neonatal Respiratory (%) Survival to Discharge (%) Pediatric Respiratory (%) Survival to Discharge (%) Circuit clots 37 54 29 58 Cannula problems 13 56 13 58 Hemolysis (pHb 50 mg/dL) 15 40 13 50 Cannula site bleeding 12 62 16 59 CNS hemorrhage 10 38 25 Renal replacement therapy 31 46 37 49 Inotropes on ECMO 33 59 28 52 Hypertension 57 14 63 Infection on ECMO 39 10 52 Mechanical Patient CNS, Central nervous system; ECMO, extracorporeal membrane oxygenation; pHb, polyhydroxybutyrate Modified from International Extracorporeal Life Support Registry, 2019 Bleeding Bleeding as a result of the systemic heparinization required with ECMO is the major complication associated with ECMO.145–147 Whereas bleeding most commonly occurs from cannulation or surgical sites, ICH is the most dreaded Intracranial bleeding occurs in approximately 11% of patients overall, with the rate highest in neonates and lowest in adults Bleeding that occurs outside of the head that cannot be controlled with medical means requires surgical investigation Although obvious risks accompany surgical intervention in a bleeding patient who has undergone systemic anticoagulation, many operative repairs have been accomplished during ECMO support Initial attempts to control bleeding focus on decreasing the rate of heparin infusion and lowering activated clotting time levels Limitation of anticoagulation may put the circuit at risk for increased clotting, especially at lower flow levels This risk must be balanced against the bleeding risk Medications to help prevent clot breakdown in the patient also are used Historically, aminocaproic acid, an antifibrinolytic amino acid that displaces plasminogen from fibrin and inhibits clot breakdown, has been the predominant medication used during ECMO Although a wide range of doses are used, the common scheme is to administer 100 mg/kg as a load followed by an infusion of 25 to 50 mg/kg per hour Despite being used in ECMO centers for many years, a randomized controlled trial of aminocaproic acid versus placebo in neonates found no difference in the need for transfusion or circuit changes due to thrombosis.146 Other reports have noted a decrease in transfusion requirements in patients with CDH patients Tranexamic acid is also used in some patients, usually at a dose of mg/kg bolus followed by mg/kg per hour.147 Several recent reports of intractable bleeding on ECMO have commented on the benefits of factor VIIa, although the data regarding this medication are still too sparse to recommend it without further investigation In a recent study, use of factor VIIa was effective in decreasing chest tube bleeding from 47 to 10 mL/kg per hour in four patients with refractory hemorrhage.148–150 Major thrombosis was noted in two patients who received recombinant factor VIIa therapy Other centers have reported decreased bleeding with lower doses of recombinant factor VIIa administration; they have administered 40 mg/kg and then increased the dose to 90 mg if bleeding continued Anecdotal reports of major and life-threatening thrombosis with factor VIIa are more frequent than those found in the literature; it should not be used until other methods of bleeding reduction, including careful assessment that surgical hemostasis has been achieved, have failed Use of AT during ECMO has also been popular over the past few years While replenishment of abnormally low AT levels may make physiologic sense, data showing that this is effective in limiting bleeding, thrombosis, heparin exposure, or changing outcome are lacking outside of small, single-center reports The expense of this medication is also an important factor to consider Discontinuation of anticoagulation to help control intractable bleeding can be beneficial and has been used for variable periods, up to days or more, without significant clotting in the ECMO circuit Risk of circuit thrombosis is reduced at higher flow rates; thus, this practice is often undertaken in larger patients.151 If anticoagulation is held or antifibrinolytics administered, it is wise to have a backup circuit readily available should clotting occur that necessitates emergent replacement of the ECMO system Infection Infection is another potential complication of ECMO.152–154 Colonization of indwelling catheters, selective adherence of bacteria to polyurethane surfaces, sequestration of bacteria from the body’s normal antibody and phagocytic defense mechanisms, and the patient’s prior debilitated state are all factors that may increase the risk of infection Successful therapy may be difficult without eliminating invasive equipment, most significantly the ECMO catheters Although sepsis (which was either preexisting or developed as the patient underwent ECMO) was once seen as a reason to exclude 676 S E C T I O N V Pediatric Critical Care: Pulmonary patients from ECMO support, support for severe septic shock is now common.155,156 Detecting a new infection in an ECMO patient is often difficult, as conventional biomarkers such as leukocytosis are nonspecific, and fevers are often masked because of targeted temperature management that is achieved via ECMO There is little evidence that obtaining routine surveillance cultures on ECMO is beneficial Clinicians must rely on meticulous clinical examination and maintain a low threshold to institute therapy if new infection is suspected The role that inflammatory markers such as procalcitonin or C-reactive protein have in monitoring infection during ECLS is unclear Serial measurements may be useful to follow response to therapy in patients with known infection Prophylactic antibiotics without a known treating source are generally not recommended, although some reports have noted a decrease in fungal infections with prophylactic antifungal agents Vascular Injury The procedure of cannulation entails placement of a large vascular cannula, imposing the risk of injury to the vessel or failure to complete cannulation These complications may be more common in percutaneous cannulation, as the vessels are not directly visualized, but they can occur during surgical approaches as well Vascular injury can present as posterior perforation with extravascular placement, subintimal placement, or vessel transection Failure to complete cannulation may result from an attempt to place a cannula larger than the vein can accommodate or from placement of the guidewire in a tributary rather than in the major vessel These will usually require surgical exploration and management A retroperitoneal hematoma has been described in patients with a history of difficult access or multiple attempts at cannula placement Other Management Tidbits Right Ventricular Failure In patients cannulated for VV support, right ventricular failure can occur, usually after several weeks of support Whether this results from an increase in pulmonary artery hypertension from fibrosis, response to the ventricle at high-pressure blood flow from ECMO inducing dilation and failure, or other causes is not clear However, this condition can occur rapidly and lead to cardiac arrest or need for emergent transition to VA support In larger patients, bypass of the right ventricle with the specialized Protek Duo cannula (LivaNova Inc.) may be useful This dual lumen cannula (29 Fr) can provide up to L of flow and is placed via the right IJ vein to the pulmonary artery The drainage port sits in the right atrium and the return lumen in the pulmonary artery, allowing for bypass of the right ventricle While it is too large for small children, it may function well in adolescents or larger children Outcomes From Extracorporeal Life Support Over 112,000 patients from all age groups who have undergone extracorporeal support have been reported to the ELSO registry as of January 2019 (see Table 56.3).9 Contemporary outcomes in various groups and diagnostic categories are shown in Table 56.4.157–166 Medical Outcomes Cervical VA ECMO is associated with risk of emboli from the ECMO circuit into the brain and potential risk for neurologic abnormalities or stroke later in life Sixty-four percent of patients younger than 18 years reported to the ELSO registry from 2008 to 2013 received cervical cannulation, with 39.7% of these patients comprising neonates Other sites included the femoral artery in 4% and the aorta in 32% Historically, carotid artery cannulation is associated with a higher rate of stroke and neurologic complications.158–160 Despite the fact that severe respiratory failure is the most common indication for ECMO in the neonatal period, airflow obstruction in survivors at school age and adolescent age is usually mild Patients with CDH are a subgroup in which lung function seems to deteriorate as children get older.161 Risk factors for persistent airflow obstruction after neonatal ECMO are diagnosis of respiratory distress syndrome, CDH, prolonged duration of ECMO treatment, and chronic lung disease Sensorineural hearing loss has also been reported in neonatal ECMO survivors Its prevalence varies among different studies, and risk factors seem to be related to neonatal intensive care treatment, such as the use of aminoglycosides, neuromuscular blocking agents, and loop diuretics rather than ECMO treatment itself In a group of 169 neonatal ECMO survivors (both with and without acute kidney injury), proteinuria as at least one sign of chronic kidney disease and/or hypertension was observed in 54 (32%) of children at a mean age of years.162 Neurodevelopmental Outcomes The greatest burden affecting quality of life and participation in society seems to arise from neurodevelopmental morbidity.163–168 This remains an understudied area In general, 5% to 10% of ECMO survivors are unable to fulfill validated assessments that compare developmental outcomes with that of healthy peers This means that the published prevalence of neuropsychological problems likely underestimates the overall neurodevelopmental outcome Data on motor function performance after neonatal ECMO is scarce, but problems in this domain occur in approximately 40% of preschool-age children Most problems are seen with gross motor function Deterioration of motor function performance has recently been shown in a longitudinal evaluation: the proportion of children with normal motor function performance declined from 73.7% at years to 40.5% at 12 years Children with low parental socioeconomic status, those with intracranial abnormalities, and those who need prolonged initial hospitalization are at risk for motor function problems at a later age Interestingly, 8-year-old children who underwent neonatal ECMO and who have mild motor function impairments and diminished PedsQL scores feel satisfied with their motor and social competence Despite an overall average cognition, however, many children (up to 50%) have special educational needs Observed problems in neonatal ECMO survivors revealed that, at school age, children have problems with working speed, visuospatial memory, verbal memory, and sustained attention and concentration.169 Another recent, easily established method of assessing neurologic function is with the Functional Status Scale (FSS) Obtained by general visual inspection of the patient or chart review, six domains of functioning are assessed In one report of 282 ECMO survivors, 89 (31%) had good, 112 (40%) mildly abnormal, 67 (24%) moderately abnormal, and 14 (5%) severely or very severely abnormal function at hospital discharge Among neonates, the development of renal failure and longer hospitalization were independently associated with worse FSS scores Chronic conditions, prematurity, VA ECMO, increased red cell transfusion in the first 24 hours of ECMO, and longer ECMO duration were independently associated CHAPTER 56 Extracorporeal Life Support with mortality Among pediatric patients, chronic neurologic conditions, tracheostomy or home ventilator, ECPR, hepatic failure, and longer ICU stay were independently associated with worse FSS scores Chronic cardiac conditions, hepatic failure, and neurologic or thrombotic complications were independently associated with mortality Achieving blood lactate concentration of mmol/L or less during ECMO was independently associated with survival in both 677 neonatal and pediatric patients.170 Precision of the FSS may be improved over the Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores Neurologic complications in cardiac patients who undergo ECMO parallel those of patients who have respiratory failure Brain death occurred in 4% of patients, 3% had intracranial infarct, and 6% had ICH Because many cardiac patients are in TABLE Suggested Long-Term Follow-up After Neonatal Extracorporeal Membrane Oxygenation 56.8 Assessments Infancy Kidney function 0–2 years School age 6 years Hypertension, urinary protein-to-creatinine ratio Referral to nephrologist (CKD) Early referral to audiology MRI of brain Early recognition, rehabilitation Mental development Early referral Motor development Referral to physical therapist Growth (mainly CDH) Referral to dietitian Kidney function 2–5 years Relevance/Intervention Referral to dietitian Hearing assessment Neurologic assessment, including imaging Preschool age Domains of Interest Growth Hypertension, urinary protein-to-creatinine ratio Referral to nephrologist (CKD) Neurologic assessment Rehabilitation Language development Hearing assessment, referral to speech-language pathologist Motor development Referral to physical therapist Growth (mainly CDH) Referral to dietitian Kidney function Hypertension, urinary protein-to-creatinine ratio Referral to nephrologist (CKD) Lung function assessment Spirometry Evaluate reversibility of airflow obstruction Motor development Referral to physical therapist Exercise capacity Sports participation and/or exercise training Neuropsychological assessment Referral to early school support Intelligence (only once in follow-up) Memory Referral to cognitive rehabilitation Attention/concentration/information-processing Behavior assessment Hyperactivity Referral to support/guidance Somatic problems ADOLESCENCE Growth (mainly CDH) 12 years Kidney function Motor function Referral to dietitian Hypertension, urinary protein-to-creatinine ratio Gross motor function (e.g., ball skills) Referral to nephrologist (CKD) Referral to physical therapist/sports participation Exercise capacity Sports participation/exercise training Neuropsychological assessment Referral to school support Career support/choice of profession Memory Referral to cognitive rehabilitation Attention/concentration/information processing Behavior assessment Hyperactivity Depressed feelings/social problems Somatic problems CDH, Congenital diaphragmatic hernia; CKD, chronic kidney disease; MRI, magnetic resonance imaging Referral to support/guidance ... data showing that this is effective in limiting bleeding, thrombosis, heparin exposure, or changing outcome are lacking outside of small, single-center reports The expense of this medication is... morbidity.163–168 This remains an understudied area In general, 5% to 10% of ECMO survivors are unable to fulfill validated assessments that compare developmental outcomes with that of healthy peers This... accessed via a Gore-Tex graft or one made of a similar material sewn into the side of the vessel This graft is tied off at decannulation Vessels accessed percutaneously are not usually ligated