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J Thorac Cardiovasc Surg 2007;133:339-345
© 2007 The American Association for Thoracic Surgery
Cardiopulmonary Support and Physiology |
a General Thoracic Surgical Experimental Laboratory, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
b Department of General Thoracic Surgery, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
c Department of Pulmonary Medicine, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
d Department of Anesthesiology, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
e Fundatió Clinic, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
f Institut d’Investigations Biomèdiques August Pi i Sunyer (IDIBABS), Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
Read at the Eighty-sixth Annual Meeting of The American Association for Thoracic Surgery, Philadelphia, Pa, April 29-May 3, 2006.
Received for publication May 15, 2006; revisions received August 20, 2006; accepted for publication September 5, 2006. * Address for reprints: Paolo Macchiarini, MD, PhD, Department of General Thoracic Surgery, Hospital Clinico de Barcelona, University of Barcelona, c. Villarroel 170, E-08036 Barcelona, Spain (Email: pmacchiarini{at}clinic.ub.es).
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Abstract |
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METHODS: Ten pigs were ventilated for 4 hours (respiratory rate, 20-25 breaths/min; tidal volume, 10-12 mL/kg; fraction of inspired oxygen, 1.0; positive end-expiratory pressure, 5 cm H2O). Thereafter, the interventional lung assist device was surgically connected to the right axillary artery and vein by using direct cannulation (n = 5) or end-to-side ringed polytetrafluoroethylene graft interposition (n = 5), and ventilatory settings were reduced to achieve near apneic ventilation (respiratory rate, 4 breaths/min; tidal volume, 1-2 mL/kg; fraction of inspired oxygen, 1.0; positive end-expiratory pressure, 20 cm H2O). Hemodynamic and intrathoracic volumes and lung cytokine levels were measured.
RESULTS: Blood flow through the interventional lung assist device was 1.7 ± 0.4 L/min or 30% ± 14% of the cardiac output, and the mean pressure gradient across the interventional lung assist device was 10 ± 2 mm Hg. The interventional lung assist device allowed an O2 transfer of 225.7 ± 70 mL/min and a CO2 removal of 261.7 ± 28.5 mL/min. Although the amount of blood flow perfusing the interventional lung assist device was significantly higher (P < .01) with direct cannulation (2.1 ± 0.3 L/min) compared with that seen in graft interposition (1.3 ± 0.3 L/min), the latter allowed similar respiratory support with reduced hemodynamic instability.
CONCLUSIONS: The axillary vessels are a safe and attractive cannulation site for pumpless partial respiratory support. Compared with direct cannulation, graft interposition was equally able to support the interventional lung assist device–driven gas exchange requirements during apneic ventilation with better hemodynamic stability.
= tumor necrosis factor ; TV = tidal volume
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Introduction |
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Unfortunately, this site and the commonly used high-flow cannulae are unsuitable for clinical long-term or ambulatory support because of the potential morbidity (eg, pericannula thrombosis, leak, dislodgments, intimal tear, and dissection) and reduced patient compliance (eg, deambulation and mobilization). A hypothetical solution would be to use the axillary vessels, an access increasingly used in cardiothoracic surgery.2-6
The pumpless extracorporeal interventional lung assist device (iLA; Novalung; Novalung GmbH, Hechingen, Germany) is a new AL powered uniquely by means of arterial pressure that drives blood flow through a femofemoral shunt created by percutaneous arterial and venous cannulation with low-resistance cannulae, thus avoiding the need for a mechanical blood pump. This device allows complete CO2 removal and minimal oxygenation and has been successfully used thus far as a bridge to lung recovery7,8 and transplantation.9 Because of these backgrounds, we investigated the safety and feasibility of attaching the iLA to the axillary vessels either by means of direct cannulation or graft interposition and the capability of either access to provide respiratory support during apneic ventilation in pigs.
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Materials and Methods |
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Study Design
Animals were ventilated with volume control (Servo 900D; Siemens, Munich, Germany) for 4 hours with the following respiratory settings: respiratory rate, 20 to 25 breaths/min; tidal volume (TV), 10 to 12 mL/kg; fraction of inspired oxygen (FIO
2), 1.0; and positive end-expiratory pressure, 5 cm H2O. After this observation period (4 hours), the right axillary artery and vein were surgically connected to the iLA through either direct cannulation (group 1, n = 5) or graft interposition (group 2, n = 5), and the ventilator parameters were modified to achieve a near-static (or apneic) ventilation, targeting a respiratory rate of 4 breaths/min and a TV of 1 to 2 mL/kg while maintaining the same FIO
2 and gradually increasing the positive end-expiratory pressure to 20 cm H20. The study was completed after this 8-hour period. Assignment to either group was aleatory and independent of the diameter or rigidity of the vessel.
Anesthesia and Monitoring
Animals were premedicated with intramuscular azaperone (4 mg/kg) and intravenous thiopental (10 mg/kg) and relaxed with intravenous rocuronium (6 mg · kg–1
· h–1). Orotracheal intubation was obtained through a 7.5F endotracheal tube under bronchoscopic guidance. Anesthesia was maintained by means of continuous infusion of fentanyl (1 µg · kg–1
· h–1) and propofol (3-5 mg · kg–1
· h–1) until the study end. Antibiotic therapy included 2 g of intravenous cefazolin at induction of anesthesia. Animals were instrumented with an arterial pressure line (5F) placed transcutaneously in the right femoral artery (PiCCO plus; Pulsion Medical Systems, Munich, Germany) and several peripheral venous catheters and a Swan-Ganz catheter (Edwards Lifesciences, Munich, Germany) placed transcutaneously in the left internal jugular vein. Peripheral oxygen arterial saturation was continuously monitored with a pulse oximeter (BCI, Inc, Waukesha, Wis) placed at the pig’s tail and another probe placed on the right arm. Urine output was continuously monitored by placement of a percutaneous bladder catheter. Temperature was maintained at 37°C with heaters and blankets. Intravenous 0.9% NaCl fluids and vasoactive drugs were given if systemic systolic arterial pressure decreased to less than 100 mm Hg, as was intravenous atropine (0.5-1 mg) if heart rate was less than 50 beats/min.
iLA Implantation Technique
Under sterile conditions, a 6- to 10-cm incision over the equivalent of the human right deltopectoral groove allowed easy exposure and encirclement by an umbilical tape of the subclavian and axillary vessels, taking care to preserve the infrascalenic portion of the brachial plexus. This site was used because of our previous hemodynamic and surgical experience.10 Proximal and distal control of the axillary artery was gained, and the umbilical tape was passed through a tourniquet. After systemic heparinization (20 IU/kg), femoral artery clamps were used proximal and distal to the cannulation or implantation site.
In group 1, after a transversal arteriotomy, the axillary artery (15F) and vein (17F) were cannulated with specially designed, short, straight, low-resistance cannulae (Novaport; Novalung GmbH, Hechingen, Germany; Figure 1). The tourniquets were tightened and secured, flow was evaluated on the basis of antegrade or back bleeding, and, if adequate, the cannulae were clamped. The distal arterial clamp was left in place until the end of the study period, and the perfusion of the distal arm was controlled clinically and with the previously placed pulse oximeter. In group 2 a 1- to 2-cm vertical arteriotomy and venotomy were created, and two 8-mm ringed polytetrafluoroethylene (Jotec GmbH, Hechingen, Germany) grafts of 3 cm in length were sewn onto the artery and vein in an end-to-side fashion by using vascular parachute techniques and 5-0 or 6-0 polypropylene sutures (Prolene; Ethicon, Inc, Somerville, NJ; Figure 2) and ultimately connected to the iLA system through silicone straight 1/4 x 3/8 rubber connectors (Novalung GmbH). The iLA device and tubing system were completely deaired and filled with normal saline solution (approximately 240 mL). Finally, the tubes were connected to the cannulae or silicone connectors, and the proximal clamps were slowly removed to create a peripheral arteriovenous shunt. A sweep gas tube providing pure O2 (6-12 L/min) was connected to the iLA and placed at the bedside (Figure E1). Functional control was achieved through a monitor (Blood Flow Monitor, Novalung GmbH), which calculates blood flow through the system by using an ultrasonic flow probe (NovaFlow System, Novalung GmbH) placed at the venous cannula. iLA malfunction was defined as a driving blood flow of less than 0.5 L.
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Hemodynamics and Lung Function
The following hemodynamic variables were measured hourly (monitor, Hewlett Packard model 685): heart rate, cardiac output (CO), cardiac index, mean arterial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure, systolic index, systolic volume, systemic vascular resistance, pulmonary vascular resistance, left ventricular systolic work, right ventricular systolic work, and body temperature through the Swan-Ganz catheter. PiCCO allowed us to measure the extravascular lung water volume, intrathoracic blood volume, and ventricular contractibility. Ventilator parameters, including minute ventilation, lung compliance, and peak inspiratory pressure, and arterial and venous blood gases were evaluated hourly as well.
Lung Cytokine Assays
The left lung was lavaged with 40-mL aliquots of sterile saline solution (0.9% NaCl) instilled through the bronchoscope’s channel and subsequently aspirated manually before intubation and every hour thereafter. Tumor necrosis factor (TNF-), interleukin (IL) 6, and IL-8 levels were measured in bronchoalveolar lavage supernatants by using an enzyme-amplified sensitivity immunoassay based on the quantitative immunometric sandwich enzyme immunoassay technique (Medgenix Diagnostics, Fleurus, Belgium) and PerSeptive (Framingham, Mass). Normal concentration values in our laboratory are as follows: TNF-, 25 to 120 µg/mL; IL-6, less than 39 µg/mL; and IL-8, less than 62 µg/mL.
Histopathologic Features
Animals were killed 4 hours after iLA implantation or if the animal’s condition was deteriorating, by using an intravenous bolus of fentanyl and propofol and potassium chloride (40 mEq). Systemic heparin (100 IU/kg) was also given to avoid postmortem thrombus formation. The lung tissue samples of each lobe were dissected and placed in formalin for 18 hours and then in 70% methanol for 24 hours. Paraffin-embedded lung sections measuring 5 µm were mounted on slides and stained with hematoxylin and eosin. Each section was evaluated to search for acute/chronic interstitial or alveolar inflammation, alveolar edema, and the presence of macrophages, desquamative cells, or polymorphonuclear intra-alveolar cells. Also, infarction or clots in the lung were evaluated. Cannulated or grafted vessels were evaluated for the presence or absence of emboli or thrombi or intimal injury.
Statistical Analysis
Continuous variables were compared by using the independent-samples t test. The odds ratio was calculated to perform between-group comparisons of categoric variables. Results are presented as means ± standard error of mean. Analyses were made with the SPSS package (version 7.0; SPSS, Inc, Chicago, Ill).
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Results |
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The overall blood flow perfusing the iLA was 1.7 ± 0.4 L/min or 30% ± 14% of the CO (7.2 ± 2.6 L/min), and iLA declamping induced a peripheral arteriovenous shunt effect (Table E1) that was well tolerated clinically. The mean resistance of the iLA was 10 ± 2 mm Hg. The iLA device supported a mean O2 transfer and AVCO2R of 225.7 ± 70 mL/min and 261.7 ± 28.5 mL/min (Figure 3), respectively, and permitted a significant reduction of the ventilatory settings to reach a near-apneic ventilation status (Table 1). Direct cannulation permitted a significantly higher arterial inflow through the iLA device than graft interposition (2.1 ± 0.3 vs 1.3 ± 0.3, P < .01, Figure E2) throughout the entire study period, whereas the latter provided similar iLA-driven respiratory support (Table 2) and more hemodynamic stability (Table E2) during apneic ventilation.
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Discussion |
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and recent progress1 suggests a high likelihood of success for ambulatory and extracorporeal devices that can be switched in and out, as in a dialysis setting, with11 or without1 an integrated pumping system. However, the clinical feasibility and advantages of pumpless devices to provide effective gas exchange when placed in parallel with the native circulation, either centrally (pulmonary artery to left atrium) or peripherally (usually femoral artery and vein, AVCO2R), have been demonstrated experimentally and clinically.7,12-16
The iLA device is a relatively new, commercially available, low-resistance membrane lung designed for pulsatile blood flow with tight diffusion membranes and a protein matrix coating, incorporating a gas exchange surface of 1.3 m2. Because the mean pressure gradient of the Novalung cannulae and device is approximately 7 mm Hg with a blood flow of between 0.5 and 2.5 L/min, it can be powered solely by the mean arterial pressure when placed peripherally through an arteriovenous shunt created by percutaneous arterial and venous cannulation with low-resistance cannulae.8 Because oxygenation is essentially uncoupled from CO2 removal, the iLA has successfully been used to allow and optimize advanced lung protective ventilation strategies beyond ARDSnet17 in patients with adult respiratory distress syndrome (ARDS)7 and CO2 retention syndromes without ventilator-associated lung injury, in recovery from lung injuries, and as a bridge to transplantation.8,9 The iLA has also been used in general thoracic patients as intraoperative respiratory support or to treat postoperative noncardiogenic ARDS (personal communication). However, because of its simplicity, low invasiveness, no need for pump support, and access through peripheral vessels, the iLA might have much wider application in an ambulatory configuration as a bridge to transplantation or as an alternative to transplantation (long-term palliation). The minimal O2 transfer is an obvious limitation of the arteriovenous attachment mode, but hypoxia can be treated by means of low-flow O2 supplementation to permit O2 diffusion across the resting native lungs, either as apneic oxygenation18 or hyperoxygenation.19
Thus far, extracorporeal ALs have used either the neck (carotid artery–internal jugular vein) or groin (femoral artery and vein) circulation as the site of implantation, both of which are eventually inadequate for long-term use or in ambulatory patients. In this sense the axillary vessels might represent a valid alternative and provide several advantages. First, the subclavian or axillary vein is a routine cannulation site in an ambulatory setting. Second, the axillary artery is rarely and less diseased than the iliofemoral vessels, benefits from a rich collateral blood flow that reduces the hazards of ischemia in the upper extremity, and has already been beneficial for different cardiac open procedures2-6 and once for extracorporeal respiratory life support.20 Moreover, it can be safely cannulated either directly or through end-to-side graft interposition.6
In the present study we investigated the safety and efficacy of the axillary vessels as a vascular access site for partial extracorporeal respiratory support. The presented results demonstrate that the iLA connected through an end-to-side graft interposition to the axillary artery and subclavian or axillary vein provides respiratory support similar to direct cannulation during apneic ventilation. This finding might have various different clinical advantages; for example, tunneled and high-volume cannulae placed over longer periods of time are more likely to dislodge or induce brachiovascular injuries, can lead to infectious complications, and are less patient friendly. On the contrary, cannulation of a graft attached to the axillary artery might avoid the technical pitfalls described clinically with direct cannulation5,6 and greatly simplifies decannulation or device exchange. Indeed, the only disadvantages appear to be the extra time required at the onset to anastomose the graft to the artery (approximately 20 minutes), the occasional bleeding from the suture line, and, last but not least, that the use of the prosthetic graft anastomosed to the artery is more expensive than the provided cannulae and might become infected. However, these pitfalls could be avoided by placing the arterial cannula into a saphenous vein graft21 that had been previously anastomosed end-to-side to the axillary vessels, and this would result not only in no extra cost but also in an unlimited availability and more hemostasis.
Axillary arterial cannulation powered significantly (P = .001) more blood flow (2.1 ± 0.3 vs 1.3 ± 0.3 L/min) through the iLA than graft interposition, and this might be partly explained by the technique itself and because we did clamp the artery distal to the cannulation site during investigation. However, a long-term direct arterial cannulation is unfeasible clinically, and an arterial graft interposition would have the advantage that it would still permit optimal distal arm perfusion, thus minimizing the risks of ischemic injury of the arm and, ultimately, avoiding a compartment syndrome on reperfusion5 and allowing more hemodynamic stability because only about less than 15% of the CO would be diverted to it. In any case this blood flow difference did not affect the iLA graft-driven AVCO2R (223 ± 26 L/min) capacity or O2 transfer, which are in line with the basal exchange requirements of an adult patient (200 and 240 mL/min, respectively, at a CO of 4-6 L/min). Because no other respiratory variables were different during apneic ventilation, one might speculate that graft interposition in the axillary vessels could provide peripheral gas exchange in a variety of clinical situations in which hemodynamic stability and early mobilization, ambulation, and extubation are desired.
The bronchoalveolar lavage cytokine responses observed in this study cannot be ultimately interpreted because of the small samples. However, one might speculate that the rapid attenuation of the inflammatory response (IL-6, IL-8, and TNF-) observed during the initial ventilation strategy can be explained by the fact that the combination of apneic (TV, 1-2 mL/kg) ventilation and iLA affords a better lung protection and minimizes more lung overdistention, recruitment, and derecruitment than the ARDSnet ventilation modus (TV, 6-12 mL/kg).17 This in turn confirms previous human studies in which low (6 mL/kg) TV ventilation was associated with a more rapid attenuation of the inflammatory response in patients with acute lung injury and ARDS.22,23
In conclusion, the present study demonstrates that the axillary vessels are a safe cannulation site for extracorporeal peripheral partial respiratory support and that the iLA, once attached to this paracorporeal site, provides, with minimal surface area (1.3 m2) and shunt blood flow (approximately 30% of the CO) requirements, an almost total removal of the produced CO2 and permits near-static or apneic ventilation (TV, 1-2 mL/kg). The minimal shunt blood flow (<15% of the CO) requirements, similar gas exchange capability, and improved hemodynamic stability of graft interposition make this vascular access modality clinically more attractive than direct cannulation and might represent a further step toward ambulatory long-term AL support.
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