Anaesthesia, 1992, Volume 41, pages 48-51 APPARATUS

Initial evaluation of an intracorporeal oxygenation device

S. COCKROFT, J. KUO, M. P. COLVIN, C. T. LEWIS, R. F. INNIS

AND

P. S. WITHINGTON

Summary We describe a recently developed intracorporeal gas transfer device, its potential applications and hazards. To date, patients with potentially reversible respiratory failure have been treated with controlled oxygen therapy and positive pressure ventilation. but this treatment may itself contribute to lung parenchymal damage from barotrauma and oxygen toxicity. Total or partial extracorporeal gas exchange can be used to reduce these risks, but this treatment is complex and has SigniJicant morbidity and mortaIity. This gas exchange device has been designed to provide partial gas transfer with simplicity of insertion and use. The oxygenator lies in the vena cava to provide prepulmonary gas exchange. In preliminary studies with three calves we have shown that the device increases both mean mixed venous and arterial oxygen content and reduces mean arterial carbon dioxide tension. Key words Equipment; intracorporeal oxygenator.

Description of the apparatus A new intracorporeal and intravascular blood gas exchange device IVOX [l] (Cardiopulmonics Inc., Salt Lake City, Utah) is currently undergoing multicentre clinical trials under an investigational device exemption issued by the United States Food and Drug Administration [2]. This equipment has been developed to augment gas exchange by conventional positive pressure ventilation [3]. The IVOX consists of a polypropylene multiple fibre oxygenator (internal diameter 200 pm) placed in the vena cava for prepulmonary blood gas exchange (Fig. 1) through a single surgical venotomy. Each external fibre surface has a siloxane gas-permeable membrane coating [4] less than 1 pm thick and is treated with covalently bonded heparin to reduce potential thrombogenicity. The fibre arrangement is crimped so that turbulent blood flow over the device enhances gas transfer [5]. The IVOX is available in four adult sizes (Table I ) so that the largest possible can be used in each case without venous endothelial trauma. A controlled vacuum regulates an oxygen flow of between 1 and 3 I.min-' through the apparatus. This minimises the risk of vascular gas embolism if fibre rupture were to occur. Co-axial double lumen tubing permits gas circulation within the oxygenator through a single veno-

tomy site. Gas flows through the inner lumen towards the oxygenator tip and then into the hollow fibres.

Insertion Right internal jugular or femoral veins are recommended as insertion sites for the device. Pulmonary artery catheterisation, if required, must preceed IVOX insertion, otherwise entanglement within the oxygenator fibres may occur. An intravenous introducer sheath is inserted under asepsis, after direct venotomy. Selection of an oxygenator of the largest size is then possible using dedicated vein size templates. The fibre oxygenator is prepared for insertion within a hydration tube containing heparinised saline. This releases trapped air from the external fibre surface to minimise the risk of air embolism. An external furling device and stiffener are attached and the IVOX fibres furled to a more compact arrangement to permit ease of insertion. Table 1. Oxygenator dimensions. Product size Length; cm Furled diameter; Fr Surface area; m2

7

8

9

30 38 0.20

33 41 0.26

31 46 0.36

10

40 48

0.5

S. Cockroft, MA, FCAnaes. Clinical Research Fellow, Anaesthetics Unit, London Hospital Medical College; J. Kuo, FRCS

Registrar, Department of Cardiothoracic Surgery; M.P. Colvin, FFARCS, Consultant Anaesthetist; C.T. Lewis, FRCS, Consultant Cardiothoracic Surgeon; R.F. Innis, Physiological Measurement Technician, Royal London Hospital; P.S. Withington FFARCS, Senior Lecturer, Anaesthetics Unit, London Hospital Medical College, London El 1 BB. Accepted 15 May 1991. 0003-2409/92/010048 + 04 %03.00/0

@ 1991 The Association of Anaesthetists of Gt Britain and Ireland

48

Evaluation of an intracorporeal oxygenation device

49

Fig. 1. The IVOX apparatus. In the foreground is the fibre oxygenator within the hydration tube. The gas controller is in the background.

After the gas conduits are connected and the gas controller adjusted for adequate gas flow, gas leakage across the oxygenator is checked to prevent potential gas embolism. N o moisture should appear at the IVOX gas outlet channel; this would indicate a fibre leak. A subatmospheric pressure of 300 mmHg is applied to the oxygenator and then both gas channels are occluded. Failure to maintain this vacuum would also indicate fibre leakage. To introduce the IVOX a guidewire is advanced through the introducer sheath under image intensifier control. A femoral approach requires the wire tip to be advanced to the level of the first rib (within the superior vena cava) and an internal jugular approach necessitates advancement until the wire tip reaches the inferior caval bifurcation (level of third lumbar vertebral body). The furled IVOX is then advanced over this guidewire and its site within the right atrium and caval system confirmed. The wire is then removed and the device unfurled (Fig. 2).

Fig. 2. The IVOX fibre oxygenator in siru within the caval venous system.

oxygen content and to perform an in vitro calibration of the reflectance spectrophotometer. At 30 min intervals throughout the investigation venous samples were taken for full blood count and biochemical analysis. Each calf had a right internal jugular venotomy and a size 7 IVOX inserted under radiographic guidance. Systemic anticoagulation was with heparin (300 IU.kg-'). Function was evaluated at maximal IVOX gas flow of 2.8 I.min-I with an no2 of 0.11.

Method The research was registered with the Home Office and performed under the Animals (Scientific Procedures) Act 1986. Following 24 h starvation, general anaesthesia was induced with xylazine (0.3 mg.kg-'), thiopentone (1-2 mg.kg-') and pancuronium (0.1 mg.kg-l) in three crossbred Fresian calves whose mean weight was 103 kg. Anaesthesia was maintained by ventilation to normocapnia with 50% nitrous oxide in oxygen and 1% isoflurane through a circle breathing system. Rumenal distension was prevented by a gastric tube, and intravenous fluids were given to replace upper gastrointestinal tract losses and maintain intravascular filling pressures. Femoral arterial, central venous and pulmonary artery pressures were monitored. Cardiac output was measured by thermodilution and continual mixed venous oxygen saturation assessed by reflectance spectrophotometry (Edwards SAT-2). In addition ECG, FE'co,, Fro, and WO, oxygen (Datex) were monitored. Arterial and mixed venous oxygen saturation was measured (OSM 2 Hemoximeter, Radiometer), as was pH and gas tensions (ABL-2 Radiometer). Oxygen saturation values obtained from this calibrated oximeter were then used to calculate blood

Results Carbon dioxide elimination

A reduction in mean arterial CO, tension was observed during use of the IVOX under conditions of normocapnia (Table 2 and Fig. 3). Oxygenat ion

Figure 4 is a sample trace of mixed venous saturation, as measured by continuous reflectance spectrophotometry, against time. Ventilation with an Plo2 of 0.11 produced a stable venous saturation of 28% within 15 min which then Table 2. Blood gas parameters: effect of IVOX activation.

Paco,; kPa Cao,; ml.dl-' Cvo,; m i d - I

IVOX off mean (SEM)

IVOX on mean (SEM)

5.23 (0.28) 8.07 (0.22) 4.17 (0.08)

4.70 (0.36) 9.61 (0.08) 5.04 (0.01)

S. Cockroft et al.

Fig. 3. The effect of IVOX activation on blood gas parameters. Fig. 5. The effect of IVOX activation on mean pulmonary arterial pressure (mmHg).

I230

I300

1330

Time

Fig. 4. Illustrates the effect of IVOX activation upon SpVO, during induced hypoxaemia (FiO, 0. I I).

increased to 53% over 30 min when the oxygenator was activated. Table 2 demonstrates that use of the IVOX was associated with an increase in both mean mixed venous oxygen content (00,) and arterial oxygen content (Cao,) (Fig. 3) during induced hypoxaemia. Haemodynamic and metabolic parameters Insertion of the IVOX caused no significant change in haemodynamic variables or cardiac rhythm disturbance. However, induced hypoxaemia did increase mean pulmonary arterial pressure which was reduced by IVOX activation (Fig. 5). In addition there was no significant change in haematological (Table 3) or biochemical variables during the 400 min study.

Discussion In this calf model there was a small increase in oxygen uptake when the intracorporeal oxygenator was used during extreme hypoxaemia. The partial reversal of hypoxia-induced rises in pulmonary arterial pressure when Table 3. Haematological data.

Time (min) 0 100 200 300 400

Red cell count Platelet count mean (SEM) 10'2.1-1 mean (SEM) 109.1-'

7.77 7.94 7.81 7.75 7.88

(0.35) (0.38) (0.53) (0.34) (0.40)

522 565 549 611 603

(80) (86) (75) (7.0) (12)

the IVOX was used suggests that some physiological significance can be inferred from the small increases produced in Cvo, and Cao,. A fall in Paco, was demonstrated when the IVOX was in use. Experimental insertion of these oxygenators has not previously been performed in the calf, although its suitability as a model for cardiovascular research is well described [6]. The calf is a relatively docile animal to handle and has thoracic and cardiovascular basal indices similar to man's. However, despite the relatively high body mass, compared to man, it was not possible to site an oxygenator of greater than 0.20 m2 surface area because of anatomical variations within the jugular venous system. This therefore limited maximum possible gas exchange. It has been shown in dogs and sheep (up to 60 kg) [ I , 31 that it is possible to site oxygenators of up to 0.60 m2 surface area with transfer rates of 204 ml O,.min-' and 252 ml CO,.min-'. Compared with extracorporeal gas exchangers with surface areas in excess of 10 m2 an intracorporeal device will necessarily be limited in performance by size. In addition to increased surface area external devices use higher gas flows (6 1.min-') and have better ventilation/perfusion ratios. An increased 'capillary transit time' through the extracorporeal oxygenator interface also improves blood oxygenation [7]. Because of these limitations it is unlikely that an IVOX could offer the same support as with an extracorporeal membrane oxygenator [8, 91. Partial pulmonary support can be achieved with an extracorporeal carbon doxide removal circuit [lo] and it is possible that the IVOX could provide a similar degree of gas transfer. No significant change in biochemical or haematological parameters was detected during the 400min study period, and with systemic anticoagulation the IVOX has been in use without adverse effects in sheep for up to 19 days [2]. This contrasts with extracorporeal circuits which incorporate a higher surface area of potentially thrombogenic material. These have an adverse effect upon all cellular components, especially decreased platelet count and impaired function [ 1 I] leading to impaired haemostasis. Extended use of a n IVOX may not be associated with the severe haemorrhage that frequently accompanies extracorporeal lung assistance. The decreased surface area of the IVOX will reduce heat losses relative to external circuits and may also decrease the incidence of sepsis secondary to microbial colonisation. Complex extracorporeal circuits pose technical problems in interhospital transfer [ 121. In contrast, the relatively simple IVOX would not require a heavy electrical load and the absence of an external circuit would reduce heat losses. The

Evaluation of an intracorporeal oxygenation device IVOX could have a role in augmentation of conventional positive pressure ventilation and enable the maintenance of normal blood gas tensions while avoiding pulmonary barotrauma associated with high lung inflation pressures and positive end-expiratory pressure [13, 141. This device may permit the use of lower inspired oxygen tensions and minimise the adverse effects of higher oxygen tensions [151 on pulmonary gas transfer and compliance. The use of the IVOX in high mortality patient groups requires careful evaluation to determine if it actually contributes to improved outcome.

Acknowledgments Financial assistance for this project was provided by British Petroleum PLC. Figure 2 was reproduced with permission of Actamed Ltd. (Wakefield).

References Mortensen JD. An intravenacaval blood gas exchange (IVCBGE) device: A preliminary report. TransactionsAmerican Society for Artificial Internal Organs 1987; 3 3 570-3. MORTENSENJD, BERRY G, WINTERSS. IVOX: An intracorporeal device for temporary augumentation of blood gas transfer in subjects with acute respiratory insufficiency. Cardiac Chronicle 1990; 4: 1-6. MORTENSEN JD, BERRYG. Conceptual and design features of a practical, clinically effective intravenous mechanical blood oxygen/carbon dioxide exchange device (IVOX). International Journal of Artificial Organs 1989; 1 2 384-9. KELLERKH, SHUTISKL. Oxygen permeability in ultrathin and microporous membranes during gas-liquid transfer. Transactions-American Society for Artificial Internal Organs 1979; 25: 469-72.

51

[5] BELLHOUSE BJ, BELLHOUSE FH, CURLCM, MACMILLAN TI,

GRUMMY AJ, SPRATTEH, MACMURRAY SB, NELEMS JM. A high efficiency membrane oxygenator and pulsatile pumping system, and its application to animal trials. TransactionAmerican Society for Artificial Internal Organs 1973; 1 9 72-9. BH, FUQUA JM, SPEAKERDM, [6] WEBERKT, DENNISON Hemodynamic measurements in HASTINGS FW. unanesthetised calves. Journal of Surgical Research, 1971; 11: 383-9. [7] NUNNJF. Applied respiratory physiology. 3rd edn. London: Butterworths, 1987: 423-9. [8] HILLJD, OBRIENTG, MURRAY JJ, DONTICMY L, BRONSON ML, OSBORNEJJ, BRODE F. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock lung syndrome). New England Journal of Medicine 1972; 2% 629-34. [9] ZAPOLWH, SNIDERMT, HILLJD, FALHATRJ, BARTLETT RH, EDMONDSLH, N o m AH. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. Journal of the American Medical Association 1979; 242 2193-6. L, F%SENTI A, MASCHERON~ D, MARCOLIN R, [lo] GATTINONI FUMGALLI R, R ~ IF,, IOPECHIRO G. Low frequency positive pressure ventilation with extracorporeal CO, removal in severe acute respiratory failure. Journal of the American Medical Association 1986; 256: 881-6. [ 1 I] CONAHAN TJ. Complications of cardiac surgery. In KAPLAN JA, ed. Cardiac anaesthesia. Orlando: Grune and Stratton, 1987: 1105-22. [I21 KEE S S , SEDGWICK J, BRISTOW A. lnterhospital transfer of a patient undergoing extracorporeal carbon dioxide removal. British Journal of Anaesthesia 1991; 66: 1414. [ 131 PETERSON GW, BAIERM. Incidence of pulmonary barotrauma in a medical ICU. Critical Care Medicine 1983; 11: 67-71. [I41 BONE RC, FRANCIS PB, PIERCEAK. Pulmonary barotrauma complicating positive end expiratory pressure. American Review of Respiratory Disease 1975; 111: 921-5. WK. Oxygen toxicity in man: [15] BARBERRE, LEEJ, HAMILTON A prospective study in patients with irreversible brain damage. New England Journal of Medicine 1970; 283 1478-84.