IVOX

" / would have everie man write what he knowes and no more.'1—MONTAIGNE

BRITISH

JOURNAL

OF

VOLUME 70, No. 6

ANAESTHESIA JUNE 1993

EDITORIAL IVOX

device is furled. An IVOX houses around 1000 of these fibres, each with an internal diameter of 190 um and a wall thickness of 35 um. Gas exchange occurs across the 1-um outer layer around each fibre. This consists of cross-linked dimethyl siloxane overlying the numerous 0.3-um diameter pores in the hollow fibre. The membrane is selectively permeable to gases, but not to liquids. Each fibre is crimped to encourage turbulent flow and further improve gas exchange. Resistance to thrombosis is produced using covalently bonded heparin and a proprietary thromboresistant outer layer. The fibres provide a total gas exchange area of between 0.21 m2 and 0.52 m2 for sizes French-gauge 7-10. However, this represents less than 10% of the equivalent gas exchange area in an ECMO circuit. In the adult, the area of lung surface for gas exchange is of the order of 75 m2. Oxygen 100% is introduced through the central conduit of a coaxial gas transport tube, entering the fibres at their distal end. Carbon dioxide exchange and oxygen transfer occur as the gases are drawn back along the length of the fibres under a subatmospheric pressure of 300 mm Hg. Waste gases and water vapour are removed via the outer lumen. The negative pressure prevents gas embolization in the event of a fibre fracturing. The IVOX is inserted as a tightly furled bundle to minimize the size of venotomy required and; it then expands to fill the inferior vena cava (IVC) and part of the superior vena cava. In the current clinical study, 89% of devices have been inserted via the right common femoral and 11 % via the right internal jugular veins [personal communication, Cardiopulmonics]. It is important that the largest possible device is used. This has been emphasized by High and colleagues [4] and so it is recommended that the vein is assessed by ultrasound before insertion of the device. An obturator with a haemostatic valve and Jtipped guidewire are introduced and the position checked with an image intensifier. The device is advanced to occupy the entire length of the inferior and superior venae cavae and it is then unfurled to lie loosely within the venous lumen. The widest diameter of the device lies at the level of the intrahepatic IVC. The venotomy is repaired, a bacterial filter is connected to the oxygen inlet and a water trap inserted in the outlet tubing to protect the flow controller. The dose of heparin administered should produce an activated clotting time of no more than 250 s or partial thromboplastin time of 80-90 s. Systemic antibiotic prophylaxis is prudent. The role of a pulmonary artery catheter (PAC) in situ, with the potential difficulties of entanglement,

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IVOX (Cardiopulmonics, Salt Lake City) is the registered acronym for an i.v. oxygenator. The device is undergoing Phase II evaluation of efficacy as part of the management of acute respiratory failure (ARF) in designated centres in Europe and the U.S.A. IVOX acts as a "lung assist" using hollow fibres for intracorporeal gas exchange and is designed to lie freely within the lumen of the superior and inferior venae cavae. The drive to develop IVOX has been stimulated by the progressive limitation of the lungs to effect gas exchange in some cases of advanced lung injury and adult respiratory distress syndrome (ARDS). Mechanical, positive pressure or high frequency ventilation techniques are the mainstays of ventilatory support in acute respiratory failure. The pathophysiology of advanced lung injuries with increased microvascular permeability and disruption of alveolar architecture leads to a loss of area for gas exchange. In addition, there is evidence that large tidal volumes and positive pressure applied to the airways contribute to this pathology by increasing alveolar oedema and capillary rupture [1, 2]. The initial search for alternative methods of gas exchange led to the development of extracorporeal membrane oxygenation devices (ECMO). However, with these devices it is necessary to use large extracorporeal blood flows and full systemic anticoagulation. In addition, ECMO requires the continuous presence of perfusionist expertise and the technique is therefore limited to specialist referral centres and for short periods of operation only. More recently, however, advances in the technology of hollow fibres and gas exchange membranes have made artificial intracorporeal oxygen transfer feasible. Mortensen [3] developed these techniques and commenced clinical studies of the safety of IVOX in 1989. These early investigations showed no IVOXrelated complications in 20 patients. Ideally, such a device should comprise a hollow fibre oxygenator, capable of being inserted through a small peripheral venotomy so as to contribute significantly to gas exchange in the venous system. It should not induce thromboembolism or intimal damage and not necessitate full systemic anticoagulation. In addition, it should not impair caval blood flow. Most of these criteria are met by the IVOX device currently available. The basic functional component is the hollow fibre. Each fibre is a polypropylene former, 35-45 cm in length, depending on the size selected; sizes range from French-gauge 7 to French-gauge 10, related to the transverse diameter in millimetres when the

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ventilatory support. Absolute contraindications are the inability to use anticoagulants safely, persistence of a low cardiac output or identification of bacteraemia or thrombus in the peripheral veins. The future role of IVOX depends on hollow fibre membrane development and on refinements of technique such as placement of devices to improve oxygenation in mixed venous blood in the superior cava and even the pulmonary artery itself. The outcome of current multicentre trials is awaited with interest. There will inevitably be problems in matching controls as in ECMO studies. However, the preliminary data (150 implants to date) suggest that the technique requires little more expertise than, for example, continuous flow renal support. It has the advantage of a longer duration of operation than ECMO: the mean duration of use in the current studies is 5.2 days, with a maximum of 29 days [personal communication]. Outcome data are not available yet, but preliminary results suggest early improvements in gas exchange and a reduction in the intensity of ventilator support. The technique may prove to be useful in maintaining life whilst lung injuries resolve, by helping to limit any detrimental effects of long-term mechanical ventilation. J. Skoyles and M. Pepperman Leicester REFERENCES 1. Dreyfuss D, Soler P, Bassett G, Saumon G. High inflation pressure pulmonary edema; respective effects of high airway pressure, high tidal volume and positive end-expiratory pressure. American Review of Respiratory Disease 1988; 137:

1159-1164. 2. West JB, Tsukimoto K, Mathieu-Castello O, Prediletto R. Stress failure in pulmonary capillaries. Journal of Applied Physiology 1991; 70: 1731-1742. 3. Mortensen JD, Berry G. Conceptual and design features of a practical, clinically effective intravenous mechanical blood oxygen/carbon dioxide exchange device (IVOX). International Journal of Artificial Organs 1989; 12: 384-389. 4. High KM, Snider MT, Richard R, Russell GB, Stene JK, Campbell DB, Aufiero TX, Thieme GA. Clinical trials of an intravenous oxygenator in patients with adult respiratory distress syndrome. Anesthesiology 1992; 77: 856-863. 5. Kallis P, Al-Saady Naab M, Bennett D, Treasure T. Clinical use of intravascular oxygenation. Lancet 1991; 337: 549.

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has yet to be fully evaluated. The principal advantage of using a PAC in the presence of an IVOX is that changes in pulmonary blood saturation can give an indication of oxygen delivery when taken in conjunction with cardiac output and haemoglobin. Gas transfer has been measured more accurately using an oxygen-helium mixture and the Haldane correction principle for the input and output gas phases [4]. Carbon dioxide elimination is measured easily using a capnograph and the volume of flow from the vacuum source. The efficiency of IVOX in terms of gas exchange has been found to vary widely in vitro, in animals and in critically ill patients. It is apparent that IVOX can perform only as a lung assist device because its oxygen transfer capability is considerably less than basal requirements. The greater rates described are of the order of 140 ml min"1 [5], with comparable carbon dioxide removal. The factors limiting gas transfer may not all be related to the constraints of hollow fibre membrane technology. Because 80% of the IVOX length is positioned in the inferior vena cava, gas exchange is influenced by splanchnic flow. This may be decreased in ARDS, thereby reducing the efficiency of oxygenation [5]. There are patients whose gas exchange requirements cannot be assisted with IVOX, particularly if they have narrow veins, and it has been suggested [4] that the inability to use a French-gauge 9 or 10 device is a contraindication to IVOX therapy, as gas transfer is always inadequate. Although it is vital to insert the largest possible device, there is a risk of impeding the caval lumen, diverting venous return to the azygos and collateral systems and bypassing the oxygenator. It has been suggested therefore, that the role of IVOX is to assist gas transfer in patients receiving maximal mechanical ventilation and who have shunt fractions less than 35% [5]. ECMO would be an option for greater respiratory requirements. Other applications include the support of any potentially reversible ARF and to protect suture lines and minimize air leaks. It is predictable that it will be used for respiratory support before lung transplantation and for some patients requiring

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