We present a 15-yr-old girl who underwent interventional lung assist with Novalung® (Novalung GmbH, Lotzenaecker, Heckingen, Germany) insertion after temporary right ventricular (RV) support from extracorporeal membrane oxygenation (ECMO). The Novalung adds oxygen and removes carbon dioxide (CO2) via a pumpless, low resistance, extracorporeal membrane.1 It has previously provided ventilatory support for acute respiratory distress syndrome, a bridge to transplantation and interhospital transport. This is the first pediatric and smallest patient to use the device. Central placement (pulmonary artery to right pulmonary vein) instead of usual femoral cannulation was chosen for pressure gradient and cannula size.
A 15-yr-old girl (41 kg, body mass index 14.4) presented with 6-mo history of increasing dyspnea, fatigue, and reduced exercise tolerance. She was diagnosed with pulmonary veno-occlusive disease with echocardiographic evidence of suprasystemic pulmonary artery pressures (PAP) (i.e., RV systolic pressure exceeded left ventricular (LV) pressure). No cardiac catheterization was performed. She was managed with furosemide, warfarin, and oxygen and listed for lung transplantation. Three weeks later she deteriorated acutely with dyspnea and desaturation despite 34 L/min oxygen via high-flow nasal cannula and face mask (noncommercial system constructed by respiratory therapy). Her systemic blood pressure by cuff was 89/40 mm Hg, heart rate was 130 bpm, Spo2 79% (on 34 L/min O2), and she was too tachypneic to speak. The echocardiogram demonstrated severe pulmonary hypertension (PH) (RV systolic pressure 109 mm Hg + right atrial pressure), mild to moderate tricuspid regurgitation, reduced LV function, and reduced RV systolic function (Fig. 1). There was no intracardiac communication. She was diagnosed with hypoxemia and severe RV failure and transferred emergently to the operating room (OR) for RV decompression and treatment of hypoxemia using an interventional lung assist (Novalung) with ECMO support as a bridge to lung transplantation. Because of the increased risk of anesthesia in patients with severe PH, femoral arterial-venous ECMO under local anesthesia without sedation was planned to facilitate Novalung insertion via sternotomy. Central cannulation was chosen to optimize blood flow because her PAP was higher than her systemic blood pressure and to enable larger-sized cannulae.
After femoral vessel exposure, she became severely bradycardic, presumably because of RV failure. She was unresponsive and tracheally intubated without medications and received external cardiac compressions and epinephrine for approximately 10 min. On institution of ECMO, there was resolution of bradycardia and she was given appropriate doses of fentanyl, pancuronium, and isoflurane. A sternotomy was performed; the right ventricle was grossly dilated. Cannulae were placed in the main pulmonary artery (22 Fr EOPA, Medtronic, Minneapolis, MN) and right pulmonary vein (22 Fr DLP, Medtronic) and connected to a Novalung circuit primed with 0.9% normal saline (Figs. 2 and 3).
Epinephrine (0.01–0.09 μg · kg−1 · min−1), norepinephrine (0.01–0.1 μg · kg−1 · min−1), and 2 L of crystalloid were infused to maintain a mean pressure of 50 mm Hg on ECMO. At commencement of ECMO, near-infrared spectroscopy (INVOS®, Somanetics, Troy, MI) readings ranged 45%–65% and the blood inlet temperature was 36.4°C. The anesthesia ventilator was then switched off for 35 min to allow titration of oxygenation and CO2 excretion from the Novalung by altering sweep oxygen flow and maintaining constant ECMO flow. Titration was guided by serial arterial blood gas measurements. Anesthesia was maintained with IV propofol and fentanyl. She was separated from ECMO after 100 min and the femoral cannulae were removed.
The patient was transferred to the intensive care unit, inotropes were weaned, and she was allowed to waken. RV function improved (Fig. 4). The ongoing treatment plan for the Novalung consisted of heparin dosing to an activated clotting time of 170–190 s and fluconazole and cefazolin prophylaxis. The patient’s trachea was extubated on postoperative Day 3 with Novalung flow of 1.8–2.2 L/min and an oxygen flow of 2 L/min. The membrane was exchanged uneventfully without extracorporeal support in the OR on Day 18 because of visible clot formation and deterioration in gas exchange. She remained in hospital breathing spontaneously, eating a normal diet, and was able to ambulate with the device with no detected neurological deficit. She underwent bilateral lung transplant on postoperative Day 30 and was discharged 25 days later.
The Novalung adds oxygen and removes CO2 via a pumpless, low resistance, extracorporeal membrane. A 60–80 mm Hg pressure gradient provides adequate flow for adults.1 Pediatric patients need a similar pressure gradient to create flow, depending on the proportion of ventilatory support required. This may limit the device for smaller patients or necessitate the use of central vessels to reduce in-circuit resistance. In our patient, the elevated PAP and consequent RV hypertrophy provided the necessary driving pressure. The hypertrophied pulmonary artery in PH allows larger cannulae. Oxygen is delivered from a standard flow meter, over the exterior surface of the hollow fibers. Gas exchange occurs by simple diffusion. CO2 removal depends on device blood flow, sweep gas flow, and the patients’ arterial CO2.2 Titration of sweep gas flows must be obtained on an individual basis, because the relative contribution of the native pulmonary circulation will differ among patients. Membrane blood flow is measured by an ultrasonic sensor on the circuit.
Novalung blood flow rates range from 0.5 to 4.5 L/min. It is made from a membrane of polymethylpentene, which is resistant to plasma leakage.1 The membrane is homogenously treated with a proprietary coating method (Novalung Coating, Novalung GmbH). The total surface area available for gas exchange is 1.3 m2.1 Heat loss is minimal. The filling volume is 240 mL.3 The maximum pressure across the membrane is 200 mm Hg and the pressure decrease at 2.5 L/min is 11 mm Hg.3
In our patient, the hypertrophied RV quickly returned to a more normal size and function after the acute reduction in RV “afterload” by insertion of the Novalung. Novalung as an “RV assist device” is novel; most reports focus on primary lung failure.1,3
Fischer et al. described their experience using Novalung for severe refractory hypercapnia in 12 adult patients awaiting lung transplantation. The duration of support was 15 ± 8 days (4–32 days) and 10 of 12 patients survived to transplant.3 Previous treatment meant using ECMO with its concomitant risks of hemolysis, infection, renal insufficiency, and bleeding complications.3,4 Lung transplant after ECMO has a perioperative mortality of 60%.3 Bein et al.1 reported use in 90 adults with acute respiratory distress syndrome as a lung “protection strategy” from ventilatory trauma. Zimmermann et al.5 describe interhospital transport of eight adult patients with severe lung failure using the Novalung.
Pulmonary veno-occlusive disease is an uncommon cause of PH that preferentially affects postcapillary pulmonary vasculature. First described by Hora in 1934, there were approximately 150 reported cases in 2000.6 Pulmonary function tests are variable. The diffusing capacity for carbon monoxide is often decreased and alveolar-arterial oxygen gradient is increased. Chest radiographs show enlarged proximal pulmonary arteries, peripheral interstitial infiltrates or septal lines, and pleural effusions in the absence of left heart failure or valvular disease. Computerized tomography shows bilateral smooth interlobular septal thickening, multifocal ground glass opacities, and pleural effusions. Usual treatments for PH in the OR (oxygen, nitric oxide, hyperventilation, prostacyclin) may precipitate pulmonary edema. In the largest series published, 6 of 11 patients deteriorated with commonly used therapy (calcium channel blockers and prostacyclin), which precipitated pulmonary edema and death.6 In those patients who initially responded to vasodilators, all but one had disease progression.6 Holcomb et al.6 advocate lung transplantation as the only proven effective treatment, because immunosuppressive and antiinflammatory regimes have not been successful. Their cohort’s outcome remained poor with 72% mortality at 1 yr (including one transplanted patient).6
Adults and children with PH have increased anesthesia morbidity and mortality with and without congenital heart disease.7 The severity of baseline PAP correlates with the incidence of complications; children with suprasystemic PAP were eight times more likely to experience a major perioperative complication than those with subsystemic PAP.7 Pulmonary vascular resistance is increased by alveolar hypoxia, hypoxemia, hypercarbia, metabolic acidosis, and sympathetic nervous system activation. RV ejection fraction may decrease acutely leading to RV failure as in our patient. In the absence of an intracardiac communication (such as a patent foramen ovale, atrial, or ventricular septal defects), right heart failure leads to decreased cardiac output and ischemia from hypoperfusion. Poor ventricular function is common in patients with pulmonary vascular disease.7 Impaired RV function is reported in 94% and reduced LV function in 20% of patients with pulmonary vascular disease.8 RV dilation can displace the septum, limiting LV filling and systemic stroke volume and cardiac output (Figs. 1 and 4). Systemic hypotension can cause a reduction in coronary perfusion and further impair RV and LV function. Hypoxemia from impaired ventilation, lung disease, and reduced pulmonary blood flow can further depress biventricular function.
Anesthesia care of these patients is difficult with no preferred technique.7 Complications are reported equally among general anesthesia or sedation and are independent of the choice of airway management.7 Tracheal intubation has been reported to precipitate pulmonary hypertensive crisis and precipitate death in critically ill adult patients with PH.7
Treatment options for our patient were extremely limited. ECMO support was used because of concerns about cardiac arrest on induction of anesthesia.7 We wanted to limit the duration of ECMO support and minimize mechanical ventilation before bilateral lung transplant. The advantages of the Novalung over ECMO are its simplicity, reductions in anticoagulation and bleeding, possibly less hemolysis, and avoidance of long-term mechanical ventilation.
This is the first pediatric case and the smallest person yet to receive a Novalung (body mass index 14/body surface area 1.29 m2), and the second time this device has been used in the emergency treatment of severe PH.9
The authors wish to thank Dr. L. Mertens, Director of the Echocardiography Laboratory, Labatt Family Heart Centre, Hospital for Sick Children and Novalung, Canada for the images, and Dr. S. Yoo, Cardiac Radiologist, Labatt Family Heart Centre, for providing the radiographic images.
1. Bein T, Weber F, Philipp A, Prasser C, Pfeifer M, Schmid FX, Butz B, Birnbaum D, Taeger K, Schlitt HJ. A new pumpless extracorporeal interventional lung assist in critical hypoxemia/hypercapnia. Crit Care Med 2006;34:1372–7
2. Zhou X, Loran DB, Wang D, Hyde BR, Lick SD, Zwischenberger JB. Seventy-two hour gas exchange performance and hemodynamic properties of NOVALUNG iLA as a gas exchanger for arteriovenous carbon dioxide removal. Perfusion 2005;20:303–8
3. Fischer S, Simon AR, Welte T, Hoeper MM, Meyer A, Tessmann R, Gohrbrandt B, Gottlieb J, Haverich A, Strueber M. Bridge to lung transplantation with the novel pumpless interventional lung assist device Novalung. J Thorac Cardiovasc Surg 2006;131:719–23
4. Duncan BW, Hraska V, Jonas RA, Wessel DL, Del Nido PJ, Laussen PC, Mayer JE, Lapierre RA, Wilson JM. Mechanical circulatory support in children with cardiac disease. J Thorac Cardiovasc Surg 1999;117:529–42
5. Zimmermann M, Bein T, Philipp A, Ittner K, Foltan M, Drescher J, Weber F, Schmid FX. Interhospital transportation of patients with severe lung failure on pumpless extracorporeal lung assist. Br J Anaesth 2006;96:63–6
6. Holcomb BW Jr, Loyd JE, Wesley Ely E, Johnson J, Robbins IM. Pulmonary veno-occlusive disease. A case series and new observations. Chest 2000;118:1671–9
7. Friesen RH, Williams GD. Anesthetic management of children with pulmonary arterial hypertension. Pediatr Anesth 2008;18:208–16
8. Vizza CD, Lynch JP, Ochoa LL, Richardson G, Trulock EP. Right and left ventricular dysfunction in patients with severe pulmonary disease. Chest 1998;113:576–83
9. Schmid C, Philipp A, Hilker M, Arlt M, Trabold B, Pfeifer M, Schmid FX. Bridge to lung transplantation through a pulmonary artery to left atrial oxygenator circuit. Ann Thorac Surg 2008;85:1202–5