Air Force Utilizes Implantable Artificial Lung

[thbarnes]

Wounded troops breathing easier, thanks to lung device

German-made Novalung now found in Air Force pulmonary emergency team's kit

By Ben Murray, Stars and Stripes

Mideast edition, Monday, July 31, 2006

Sixteen months after Lance Cpl. Joshua Mishoe nearly drowned in his Humvee in a canal in Iraq, he�s finally starting to breathe better.

He can walk short distances around his Florida home without getting out of breath and no longer needs supplemental oxygen at night, his mother said.

Improvement is slow, but it�s a far cry from where he was last March when he was lying in Landstuhl Regional Medical Center in Germany, his lungs steadily failing him, his chances of survival getting worse.

�He was dying,� said his mother, Julie Mishoe.

To save his life, military doctors looked outside their normal arsenal of medical tools and found something that would not only keep Joshua Mishoe alive, but within two months would help revive three other servicemembers.

Called an interventional lung assist and made by a German company called Novalung, the device is now part of the inventory a special Air Force pulmonary emergency team takes to Iraq when critical lung patients need aid.

But using it also placed doctors in the cross hairs of an investigation by the Office of the Surgeon General of the Army because the Novalung machine hadn�t made its way through the lengthy American regulations process required to approve medical devices for use.

http://www.stripes.com/article.asp?section...p;article=39016

[chbare]

Here is a link to an abstract on this device. You will have to log in for the full article.

http://www.ncbi.nlm.nih.gov/entrez/query.f...p;dopt=Abstract

Take care,

chbare.

[mediccjh]

If it works, there should be no problem. Damn American bureaucracy.

[Ace844]

For those who are interested... Here's the 'full-text,'

[web:00c7a44ea8]http://sas.epnet.com/externalframe.asp?tb=0&_ug=sid+9E699AFE%2D6895%2D437C%2DA6A6%2D7C2AE7692699%40sessionmgr5+4768&_us=SLsrc+ext+or+Date+034D&_usmtl=ftv+True+137E&_uso=hd+False+db%5B0+%2Dbyh+B26E&fi=byh_18826225_AN&lpdf=true&pdfs=&tn=&tp=PC&es=cs%5Fclient%2Easp%3FT%3DP%26P%3DAN%26K%3D18826225%26rn%3D1%26db%3Dbyh%26is%3D0267%2D6591%26sc%3D%26S%3D%26D%3Dbyh%26title%3DPerfusion%26year%3D2005%26bk%3DS&fn=1&rn=1&bk=S&EBSCOContent=ZWJjY8Pr5HePprBrsOvma6Gmr4GPp7WFpK65faWWxpjDpfS40OnssNOk7KzY5K2

w1+XyvwAA&an=18826225&db=byh&[/web:00c7a44ea8]

[web:00c7a44ea8]http://weblinks3.epnet.com/externalframe.asp?tb=1&_ua=bt+TD++%2231J%22+shn+1+db+byhjnh+bo+B%5F+1EDC&_ug=sid+E093B59F%2D885D%2D490A%2D8C22%2DCEB34FB59780%40sessionmgr2+dbs+byh+cp+1+61EA&_us=hd+False+fcl+Aut+sm+ES+or+Date+frn+1+mdbs+byh+sl+%2D1+dstb+ES+sel+False+ri+KAAACB2D00081095+90F4&_uh=btn+N+6C9C&_uso=st%5B0+%2DJN++%22Perfusion%22++and++DT++20051101+tg%5B0+%2D+db%5B0+%2Dbyh+op%5B0+%2D+hd+False+ED7C&fi=byh_18826225_AN&lpdf=true&pdfs=489K&bk=H&tn=11&tp=CP&es=cs%5Fclient%2Easp%3FT%3DP%26P%3DAN%26K%3D18826225%26rn%3D2%26db%3Dbyh%26is%3D02676591%26sc%3DR%26S%3DR%26D%3Dbyh%26title%3DPerfusion%26year%3D2005%26bk%3DH&fn=1&rn=2&[/web:00c7a44ea8]

(Seventy-two hour gas exchange performance and hemodynamic properties of NOVALUNG†iLA as a gas exchanger for

arteriovenous carbon dioxide removal

Xiaoqin Zhou @ David B Loran, Dongfang Wang, Brannon R Hyde, Scott D Lick and Joseph B Zwischenberger

Department of Surgery, The University of Texas Medical Branch, Galveston, Texas, USA

University Boulevard, Galveston, 77551-0528, Texas.Address for correspondence: Joseph B Zwischenberger, M.D.,

Division of Cardiothoracic Surgery, Department of Surgery, 301

E-mail: jzwische@utmb.edu

Supported in part by Novalung GmBH.

Perfusion 2005; 20: 303/308

# 2005 Edward Arnold (Publishers) Ltd 10.1191/0267659105pf838oa)

Objective: Acute respiratory failure is complicated by acidosis and altered end-organ perfusion. NOVALUNG† iLA is an interventional lung assist (ILA) device for arteriovenous carbon dioxide removal (AVCO2R). The present study was conducted to evaluate the device for short-term CO2 removal performance and hemodynamic response.

Methods: Six adult sheep received cannulation of the jugular vein and carotid artery. The ILA-AVCO2R circuit was placed on the sheep for 72 hours. Hemodynamics and PaCO2 were measured; CO2 removal was calculated while varying sweep gas flow rates (Qg), device blood flow rates (Qb), and PaCO2. Results: Hemodynamic variables remained normal throughout the 72

hour study. CO2 removal increased with increases in Qg or Qb. Mean CO2 removal was 119.3 ml/min for Qb 1 L/ min, Qg 5 L/min, and PaCO2 40/50 mmHg. PaCO2 was directly proportional to CO2 clearance (R/0.72, pB/0.001). Conclusion: NOVALUNG†iLA can provide near total CO2 removal with Qb 1/2 L/min, Qg 5 L/min, and minimal flow resistance (3.889/0.82 mmHg/L/min). PaCO2 correlates with CO2 removal and is dependent on Qb and Qg. Perfusion (2005) 20, 303/308.

Introduction

Extracorporeal membrane oxygenation (ECMO) may offer life-saving treatment of acute respiratory distress syndrome (ARDS) when conventional therapies have failed.1 ECMO, however, demands sophisticated equipment, well-trained bedside technicians,

and is complex and expensive. Blood cell trauma from the pump and blood/surface interactions requires frequent blood transfusions and may augment the systemic inflammatory response.2,3 After animal trials establishing the feasibility of

pumpless lung assist, an alternative approach has been developed primarily to remove carbon dioxide (CO2) by a membrane gas exchanger placed in a simple arteriovenous shunt while blood is oxygenated by the native lung.4 12 Arteriovenous carbon dioxide removal (AVCO2R) achieves near total CO2 clearance while allowing oxygenation by native apneic lungs in both sheep models1320 and adult humans with ARDS.19,21,22 Currently, in the United States, there is no FDAapproved, commercially available AVCO2R-specific CO2 removal device. NovaLungTM GmbH (Hechingen, Germany) has developed a small (1.3 m2 polyuropentene-fiber surface area), low-resistance gas exchanger for pumpless interventional lung

assist (ILA). The NOVALUNG†iLA system (a photo is available at http://www.novalung.com) consists of a gas exchanger specifically designed for a percutaneous arteriovenous circuit. This gas exchanger’s small size, low resistance, and efficient

gas exchange properties are ideal for AVCO2R. The arteriovenous pressure gradient drives blood through the device. Clinical use of NOVALUNG† iLA in Europe has demonstrated efficient oxygenation and CO2 removal in patients with acute respiratory failure.21,23 25 However, there is little large-animal data describing the ability of NOVALUNG† iLA to remove CO2 and maintain hemodynamic stability. Our present study aimed to systematically test the CO2 exchange capacity of the NOVALUNG†iLA and assess hemodynamic response in large animals (sheep) over a 72-hour study period.

Materials and Methods

Animals

All animals received care according to the ‘Guide for the Care and Use of Laboratory Animals (1985)’

prepared by the US Department of Health and Human Services and published by the National Institutes of Health (NIH). The study was approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Texas Medical Branch,

Galveston, with strict adherence to the IACUC guidelines regarding humane use of animals. Our management of the sheep parallels our standards for patient care. Our team, including a faculty veterinary anesthesiologist, provides bedside care 24

hours per day. Animal Resource Center personnel make daily rounds to insure animal management protocol adherence.

Surgical procedure

Adult female sheep (n/6, 3/4 years old, 35/45 kg) were given ketamine (12.5 mg/kg intramuscular, 9/5 mg/kg intravenous titrated to effect) for initial sedation. The sheep were then orally intubated with an endotracheal tube and placement was confirmed by capnometry. Three percent halothane was administered via the anesthesia ventilator

(Ohmeda 7000, BOC Health Care, Liberty Corner, NJ). Anesthesia was maintained during the surgical procedures with 1/2.5% isoflurane in 2/3 L/min oxygen titrated to a heart rate of 75/120 beats per minute. The sheep were prepped at the neck and groin and draped in the supine position. Using the Seldinger technique, a pulmonary artery/thermal dilution cardiac output catheter (Swan-Ganz, Baxter Healthcare Corp., Edwards Critical-Care Division, Irvine, CA) was introduced into the right external jugular vein. The right femoral artery and vein then were each cannulated with 16 gauge, 60-cm catheters

(Intracath, Becton-Dickinson, Sandy, UT) via a sterile cut-down for blood gas sampling, hemodynamic monitoring and intravenous infusion.

Equipment procedure

All animals initially received a tracheostomy for further anesthesia administration and ventilator assistance in recovery. All sheep were anticoagulated with intravenous heparin (initial dose 100 units/kg bovine lung heparin, Upjohn, Kalamazoo,

MI) for an activated clotting time (ACT, measured with Hemochron 400, International Technidyne, Edison, NJ) between 180/300 s. Sterile incision and cannulation (BIO-MEDICUS@ Pediatric venous cannula, Medtronic Inc., Minneapolis, MN) in the

left carotid artery (12 Fr.) and left internal jugular vein (14 Fr.) was performed. The common carotid artery was ligated distal to the cannula. The NOVALUNG† iLA was primed with 240 mL of normal saline, de-aired, and connected to the vascular cannulae. Once the AVCO2R circuit was secured to the sheep, isoflurane was discontinued. The animals were transported to the ICU for recovery, connected to a volume-controlled ventilator (Servo 900C; Siemens- Elema SoPna, Sweden) and allowed access to food and water. Gas exchange with the native lung and the ILA device was observed for 72 hours. The fraction of inspired oxygen (FiO2) was titrated between 0.4 and 1.0 and the positive end-expiratory pressures (PEEP) between 5 and 10 mmHg to maintain adequate PaO2 levels (/80 mmHg). A HP 78534B Monitor continuously monitored

systemic hemodynamic variables which included heat rate (HR), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP) and cardiac output (CO). AVCO2R circuit blood flow was measured by a real-time flow meter (HT109, Transonic Systems, Ithaca, NY) with full continuous flow as determined by the size of the arterial cannula.26 Blood flow could be regulated by a C clamp on inlet blood tubing. Mean arterial pressures in the device inflow and outflow were measured intermittently. Partial pressures of gases

in device inflow and outflow tubing were measured by the Synthesis 15 blood gas analysis system (Instrumentation Laboratory, Lexington, MA). During the 72-hour study, hemodynamic parameters, blood gases, and CO2 removal were evaluated and recorded at 0, 24, 48 and 72 hours. Prior to measuring CO2 removal at indicated timepoints, spontaneous

breathing was suppressed by boluses of intravenous pentobarbital (180/200 mg/kg) to allow for a fixed respiratory rate of 4 breaths per minute. Tidal volume was adjusted between 2 and 8 mL/kg to maintain PaCO2 between 20 and 80 mmHg to

observe the effects of PaCO2 on CO2 removal. The NOVALUNG†iLA sweep gas was 100% oxygen and the flow rate was controlled by an in-line flow regulator. Exhaust sweep gas CO2 concentration was measured in-line. Carbon dioxide clearance

was calculated based on sweep gas flow and exhaust gas CO2 concentrations. Resistance was calculated as the quotient of the pressure drop and device flow.

Statistical analysis

All data were reported as mean value9/standard deviation. The relationships between dependent and independent variables were evaluated by one way ANOVA on rank and linear regression analysis. NOVALUNG†iLA for AVCO2R

Results

During the 72-hour observation course, hemodynamic parameters (MAP, MPAP, PCWP, CVP and CO) remained within normal limits and unchanged (p/0.05, Figure 1). Mean resistance through the lung assist device was 3.889/0.82 mmHg/L/min and independent of blood flow (Qb) and sweep gas flow (Qg). There was no device thrombosis, leakage, or

other complications noted. Effect of sweep gas flow on CO2 removal With constant Qb and PaCO2, CO2 removal increased

with Qg (1/15 L/min) directly and significantly (pB/0.001), but nonlinearly. With constant Qb (1 L/min), CO2 clearance was 60.039/4.43 mL/min with 1 L/min Qg, 92.909/14.70 mL/min with 2 L/min Qg, and 120.749/26.98 mL/min with 5 L/min Qg. Only a small increase in CO2 clearance was observed (133.599/24.63 mL/min for 10 L/min Qg and 140.259/34.10 mL/min for 15 L/min Qg) for further increases in sweep gas (Figure 2). Effect of Qb on CO2 removal With constant Qg (5 L/min) and PaCO2 (40/50mmHg), Qb was incrementally increased from 0.5L/min to 1.5 L/min while measuring CO2 removal.CO2 clearance increased from 84.049/25.01 mL/min to 139.409/27.61 mL/min (pB/0.05, Figure 3). For the 72-hour period (except for temporary experimental adjustments), we set Qb (1 L/min) and Qg (5 L/min) constant. Mean CO2 clearance was

119.39/25.1 mL/min (range, 57.6 to 174.5 mL/min).The quantity of CO2 removal did not significantly change with time (Figure 4).

Effect of PaCO2 on CO2 removal

With a constant Qb (1 L/min) and Qg (5 L/min), CO2 clearance was directly proportional to PaCO2 as it was increased from 20 to 80 mmHg by hypoventilation. A significant correlation between CO2 clearance

and PaCO2 was expressed as:

CO2 Removal14:9PaCO2

2:65 (R0:72; pB0:001; Figure 5):

Discussion

The NOVALUNG†iLA system removed CO2 efficiently with a simple arteriovenous shunt. Carbon dioxide clearance was influenced by the following factors: device blood flow, sweep gas flow and arterial PCO2. At PaCO2 between 40/50 mmHg, an

increase in CO2 removal was seen as the sweep gas flow varied from 1 L/min to 15 L/min with a constant blood flow of 1 L/min. This increase became relatively less when sweep gas flow was above 5 L/min. Likewise, enhanced CO2 removal Figure 1 Hemodynamic response with time. p/0.05 (one-way ANOVA) at each time point.

Figure 2 Relationship of sweep gas flow and CO2 removal. pB/0.001 (one-way ANOVA on rank) at each time point.

NOVALUNG†iLA for AVCO2R

was shown as blood flow varied from 0.5 L/min to 1.5 L/min with a constant sweep gas flow rate of 5 L/ min. When blood flow and sweep gas flow rates were held constant at 1 L/min and 5 L/min, respectively, CO2 removal varied directly with PaCO2 (20/80 mmHg). These results show the PaCO2 level and subsequent respiratory acidosis could be controlled over a wide range of arterial PaCO2 by adjusting the sweep gas flow or blood flow rate through the device. In addition, there was no

evidence of hemodynamic instability for the 72-hour duration. Previous AVCO2R circuits have utilized commercially available gas exchange devices or ‘‘oxygenators’’ originally designed for cardiopulmonary bypass during cardiac surgery. The commercially available Affinity† (Medtronic Minneapolis, MN) device is an oxygenator with a conjoined heat exchanger. The Affinity† oxygenator consists of hollow polypropylene micropore fibers with total gas exchange surface area of 2.5 m2 and 270 ml of priming volume. AVCO2R utilizing the Affinity† has shown total removal of CO2 during acute respiratory failure and hypercapnea, normalization of arterial PCO2 and pH, and significant reductions in the level of mechanical ventilation required in both animal models4,5,7,8,10,18 and phase I clinical trials in adults with severe ARDS.19,22 The mean or median CO2 removal rates were in excess of 100 mL/min in both phase I studies. In large animal ARDS models, AVCO2R allows for decreased peak airway pressures resulting in reduced alveolar stretch, lower expression of interleukin-8, and lower rate of neutrophil translocation across damaged alveolar basement membranes.27 Decreased ventilator pressures might also ameliorate apoptosis of lung cells by down-regulating expression of tumor necrosis factor alpha (TNF-a) and proapoptotic factor.28 By providing control of PaCO2 and arterial pH, AVCO2R can attenuate the inflammatory response in ARDS and the iatrogenic damage caused by high ventilatory pressures. Clinically, these effects are manifested in patients with severe respiratory failure as an improvement in the PaO2/FiO2 ratio and reversal of CO2 retention.19 Compared to the Affinity†, the NOVALUNG†iLA has a smaller surface area (1.3 m2) of biocompatible hollow polymethylpentene fibers and smaller priming volume (240 mL) that theoretically minimizes blood trauma while maintaining an appropriate flow (around 1/2 L/ min) to surface area ratio. This smaller surface area allows near-total CO2 clearance through an arterialvenous shunt flow of only 10 to 15% of cardiac output, a flow rate we have previously shown not to affect distal organ perfusion.6 More recently, a hollow-fiber gas exchanger29,30 was designed with 1 m2 surface area that enables CO2 removal of 41 mL/min with 1 L/min blood flow

Figure 4 CO2 removal over 72 hours at blood flow of 1 L/min,

sweep gas of 5 L/min, and PaCO2 of 40/50 mmHg.

Figure 5 CO2 removal as a function of PaCO2 at blood flow of 1 L/min and sweep gas flow of 5 L/min; pB/0.001. Figure 3 Relationship of blood flow and CO2 removal. pB/0.05 (one-way ANOVA on rank) at each time point.

NOVALUNG†iLA for AVCO2R

and 3 L/min sweep gas flow. However, the higher resistance of 20/40 mmHg/L/min may limit use without the addition of a pump.31 An ambulatory AVCO2R prototype from our group is composed of ultra tight polymethylpentene hollow fibers with 2m2 surface area and removes CO2 at 104.89/14.0 mL/min for 0.9 L/min blood flow and 2 L/min sweep gas flow with a mean resistance of 2.89/0.8 mmHg/L/min.32 The NOVALUNG†iLA device compares favorably with these alternative designs with a CO2 removal rate of 119.39/25.1 mL/min at 1 L/min blood flow and 5 L/min sweep gas flow with resistance as low as 3.889/0.82 mmHg/L/min. Recently, the NOVALUNG†iLA was utilized in an arterio-venous circuit for a case of ARDS refractory to high frequency oscillatory ventilation. PaCO2 was improved from 13.3 to 9.3 KPa and pH (baseline 7.14) was normalized within 4 hours at 2.1 L/min blood flow and 12 L/min sweep gas flow.25 Based on our 72-hour study, we conclude that the NOVALUNG†iLA AVCO2R circuit achieves predictable CO2 elimination via the small and ultra lowresistance gas exchanger without hemodynamic compromise. Carbon dioxide removal increases with increased arterial PCO2 gradient and can be augmented by increasing sweep gas flow and/or blood flow rates. Use of NOVALUNG†iLA in the management of acute respiratory failure is promising and demands further clinical application and outcomes determination.

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[future medic 48_234]

Is there a picture of the novalung?

[Ace844]

Is there a picture of the novalung?

http://www.novalung.com/eng/medical_profes...iLA_therapy.asp