Severe acute lung injury (ALI) involves complex overlapping processes, including inflammation, fibrosis, necrosis, and infection, with variable functional recovery. Since the first successful case report in 1972, extracorporeal life support (ECLS) or extracorporeal membrane oxygenation (ECMO) has become a standard approach for severe respiratory failure unresponsive to other therapy.1 Over the last 10 years, ECMO has been used for pulmonary indications in more than 4,000 pediatric patients, for an average duration of 11 days, with 59% survival to hospital discharge.2 In the past, if right ventricular (RV) heart failure or no lung recovery occurred after 20–30 days of ECMO, ALI was considered irreversible, ECMO was discontinued, and the patient died.
More recently patients with severe lung disease have been maintained on ECMO for months, as opposed to days, with eventual decannulation and recovery.3–11
We report the case of a child, 7 years old, with severe inhalational burn injury and rapid progression to multisystem organ failure. She was supported by ECMO with no lung function for almost 2 years. Central nervous system was normal throughout, and lung function recovered. This is the longest successful case of ECMO and provokes further discussion regarding “irreversible” lung injury.
A 30 kg female, 7 years old, with 35% total body surface area full thickness burns and severe inhalational lung injury was transferred to our PICU on the day of injury. She was initially anesthetized and receiving mechanical ventilation with FiO2 of 0.6 and mean airway pressure (MAP) exceeding 20 cm H2O.
On hospital day seven (HD#7), during routine debridement of her burns, the patient experienced pulseless electrical activity cardiac arrest. Cardiopulmonary resuscitation was initiated and the patient achieved return of spontaneous circulation (ROSC) in 6 minutes. Despite ROSC, the patient remained hemodynamically unstable and was cannulated for veno-arterial (VA)-ECMO via her right femoral vein (17 Fr Medtronic) and left femoral artery (13 Fr Medtronic with 8 Fr distal cannula). She was maintained on ECMO support at 2.5 L/minute. This support allowed lung rest (low MAP and ventilator rate) and cardiac rest (weaning from vasoactive drugs). Cardiac function recovered by VA-ECMO day 7 but the patient developed Pseudomonas necrotizing pneumonia, resulting in severe ALI and complete lung opacification (Figure 1, A and B). On ECMO-day 7/HD#14 she was converted to veno-venous (VV)-ECMO using the same femoral venous cannula for drainage and a right internal jugular venous cannula for infusion. The period of VA-ECMO is designated as ECMO Phase 1 and the VV-ECMO period as ECMO Phase 2 (Table 1). On VV-ECMO the flow was 2 L/min with oxygen saturation (SaO2) 85%, PaCO2 40 mm Hg and satisfactory hemodynamics. The patient had no lung function with tidal volume of 1–2 ml/kg and MAP 18 cm H2O (effective compliance 1–2 ml/cm H2O). For the next 54 days, she was maintained on VV-ECMO. She experienced many complications including four additional brief cardiac arrests, septic shock, bleeding requiring massive transfusion, renal failure requiring renal replacement therapy, and circuit clotting requiring eight circuit changes. She also developed leg ischemia on VA-ECMO, despite a reperfusion cannula, and required a left below knee amputation while on VV-ECMO, on ECMO D#9.
Bronchoscopy on ECMO-D#28 revealed complete obstruction of the airway with endothelial debris, old clot, and fresh bleeding. Parenchymal lung bleeding was controlled by discontinuing heparin anticoagulation, transfusing platelets, and delivering inhaled Factor VII via bronchoscopy. Lavage with liquid perfluorocarbon cleared the airways (OriGen Biomedical, with FDA approval). Subsequent bronchoscopies revealed resolution of gross obstruction of the large and medium airways and no further pulmonary hemorrhage (Figure 2). Although sedated, the patient was cognitively intact with a normal head CT. However, there remained no measurable lung gas exchange. Total respiratory support from VV-ECMO with flow 2 L/min was required to maintain SaO2 greater than 75%. The hemoglobin was maintained at 12 gm/dL to ensure adequate systemic oxygen delivery.
During Phase 2, the patient developed gradually increasing pulmonary vascular resistance. By ECMO-D#50, there were clinical signs of RV failure, and an echocardiogram showed significant RV distension, hypertrophy, and dysfunction with systolic septal flattening. RV failure has been considered an indication of irreversible lung damage and has been used to define futility and indicate termination of ECMO support. Lung transplantation was considered but was contraindicated due to renal failure, intermittent sepsis, and difficult ambulation after leg amputation. Because lung recovery was not expected and lung transplantation was not feasible, conventional practice would have been to withdraw ECMO support. However, the patient was alert and appropriately interactive with family and caregivers. After several multidisciplinary discussions amongst family and caregivers, the decision was made to provide an RV mechanical assist device and oxygenator (RVAD-O2).
Thus, Phase 3 of the patient’s course began on ECMO-D#60. The patient was cannulated via sternotomy, with a right atrium (RA) drainage cannula and a pulmonary artery (PA) infusion cannula (15 Fr Medtronic arterial cannula via a graft for PA and 24 Fr right angle Medtronic venous cannula for RA). The cannulae were tunneled through the upper abdomen and attached to a CentriMag (Abbott Laboratories) centrifugal pump and a Quadrox (Maquet) oxygenator. Upon institution of RVAD-O2, the patient had prompt increase in SaO2 to 100% and improved cardiac output. CentriMag flow was 3 L/min and oxygenator sweep gas of 3 L/min. A tracheostomy was performed shortly after RVAD placement. The patient remained on RVAD-O2 for the next 545 days. To support lung recovery, gentle mechanical ventilation was continued with MAP less than 15 cm H2O, eventually providing tidal volume 4–5 ml/kg. Cognitively, the patient thrived. The patient learned to walk and ride a bicycle with a leg prosthesis, further promoting pulmonary rehabilitation.
On ECMO D#420, we transitioned from the CentriMag to a PediMag pump and from the Quadrox to a ped-Quadrox oxygenator, i.e., ECMO Phase 4. By ECMO-D#500, the patient’s tidal volume was 6 ml/kg, compliance was 35 ml/cmH20, and the chest x-ray was improving. RVAD flow was gradually decreased as lung function improved and pulmonary vascular resistance decreased. By ECMO-D#520, the flow was decreased from 3 L to 300 ml/min, the sweep gas was room air at 2–3 L/min, and SaO2 was 95%.
At this point, oxygenation was adequate to wean off ECLS, but sweep flow was still required for CO2 clearance. Thus, on ECMO-D#553, in ECLS Phase 5, we converted to extracorporeal CO2 removal (ECCOR). In the cardiac catheterization lab, we cannulated the RA with a 13F double lumen Avalon cannula, tunneled through the skin and attached to the PediMag pump and pediatric membrane lung. Once this was successfully achieved, we removed the RVAD-02 cannulas via resternotomy and closed the chest. CO2 clearance initially required 300 ml/min blood flow with 3 L/min sweep gas. ECCOR was continued 52 days until CO2 removal was no longer needed. Meanwhile, the patient continued aggressive physical therapy, riding her bicycle around the PICU and attending school every day. When consistently able to both oxygenate and ventilate on minimal ventilation support through her tracheostomy, it was determined the patient had recovered sufficient lung and cardiac function to remove all extracorporeal support. Thus, on ECMO-D#605/HD#612, she was decannulated.
Minimal ventilator support was continued. The patient was discharged to home on HD#662. A Passy-Muir tracheostomy valve allowed speech communication. Home mechanical ventilation was provided 24 hours a day, and peritoneal dialysis was provided 12 hours every night. Sildenafil and bosentan were prescribed for pulmonary hypertension.
By 1 year after discharge, the patient was spontaneously breathing air without mechanical assistance during the day, with CPAP of 6 mm Hg at night. At 20 months postdischarge, she did not require oxygen during the day and received nighttime CPAP. While renal failure was able to be medically managed for a few months without dialysis, with patient growth, her renal function worsened and she ultimately required a renal transplant. Renal function is now normal and she did not require any increase in respiratory support after her renal transplant. The patient has been attending school at her expected grade level, and she has resumed all activities in which she engaged before her injury.
This case provokes discussion of management of severe lung disease and the provision of long-term mechanical cardiopulmonary support. The ability of the patient’s lungs to recover from total acute failure certainly exceeded expectations and the duration of this patient’s support is the longest yet reported for ECMO. We acknowledge that this case also invites thoughtful reflection and dialogue regarding subject selection and resource utilization.
Cannulation for VA Access in Children
Neck cannulation is an alternative to groin vessel cannulation in patients above 15 kg. While this patient had suffered burns to her upper body and she was in cardiorespiratory extremis prompting the choice of groin cannulation, the risk of limb ischemia with groin cannulation is significant and should be considered when choosing the cannulation site for ECMO support.12,13
For 2 weeks after placement of the CentriMag RVAD, the circuit was maintained without anticoagulation. Resumption of heparin anticoagulation was necessary but led to thrombocytopenia and coagulopathy, with conjunctival and subcutaneous hemorrhages. Although heparin-induced antibody testing was negative, a direct thrombin inhibitor, bivalirudin, was substituted for heparin. Thrombocytopenia and coagulopathy promptly resolved. Bivalirudin was continued for the duration of mechanical cardiopulmonary support.
Intensive physical and occupational therapy enabled the patient to learn to walk with a prosthesis.
The patient attended school with one-on-one instruction 5 days a week and with virtual attendance in her own school with her classmates two times a week. This intensive level of schooling enabled the patient to remain abreast of her studies and her peers at the appropriate grade level.
There were recurrent Pseudomonas infections and persistent fungemia while the patient was in Phase 2. However, blood cultures were negative within 48 hours of RVAD conversion. The patient received prophylactic fluconazole for 18 months and had no recurrence of fungemia.
The acute pulmonary hypertension was presumable due to pulmonary fibrosis which did not respond to steroids. Serial echocardiograms and pro-BNP determinations showed gradual improvement during and after RVAD support. One month after discharge, echocardiography showed near normal RV function, and bosentan was discontinued. Sildenafil was subsequently discontinued. Six months after discharge, echocardiography showed normal biventricular function and no evidence of pulmonary hypertension.
Pigment nephropathy, septicemia, and extensive burns caused renal failure that was initially treated by VV dialysis and later by peritoneal dialysis. She received a living unrelated donor renal transplant and now has normal renal function.
This patient has experienced significant and ongoing functional lung recovery. For lung recovery from ALI to occur, there must be regeneration of lung tissue. Recent research has highlighted the impact of stress-induced lung parenchymal remodeling and growth in response to a variety of insults.7–10Although this case involves a pediatric patient, other reports demonstrate similar late recovery in adults.10,11 Recovery after months of no lung function is a recent observation made possible by mechanical lung support, stimulating basic and clinical research in lung regeneration.
The implications of this patient’s recovery raise serious questions about resource utilization (as did dialysis for renal failure 50 years ago and mechanical cardiac support 20 years ago). The resources invested in this patient cannot be readily quantified but are large in monetary terms and institutional effort. Research on moving ECMO out of the ICU, even out of the hospital, is underway.14 Promotion of ECMO leading to lung recovery, rather than reversion to lung transplantation, should be expected to lower lifelong costs and improve quality and duration of survival.
In summary, this child received 605 days of extracorporeal support for total acute lung failure and associated RV failure. She has recovered lung and heart function 3 years after profound injury, with ongoing improvement. While the full results from this case may not be consistently reproducible, it does prompt review of use and timing of central cannulation and airway clearance techniques and provides a new perspective to consider regarding the ability of lung tissue to recover or regenerate as well as the ability to safely provide long-term mechanical cardiopulmonary support.
We would like to sincerely thank Dr. Robert Bartlett for his endless support throughout this case and for his expert review of this manuscript.
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