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Ann Thorac Surg 2000;69:910-912
© 2000 The Society of Thoracic Surgeons


Original Articles

Technique of controlled reperfusion of the transplanted lung in humans

Scott D. Lick, MDa, Paul S. Brown, Jr, MDa, Mark Kurusz, CCPa, Roger A. Vertrees, PhDa, Christopher K. McQuitty, MDb, William E. Johnston, MDb

a Divisions of Division of Cardiothoracic Surgery, The University of Texas Medical Branch, Galveston, Texas, USA
b Division of Cardiothoracic Anesthesiology, The University of Texas Medical Branch, Galveston, Texas, USA

Address reprint requests to Dr Lick, Division of Cardiothoracic Surgery, University of Texas Medical Branch, Galveston, TX 77555-0528.
e-mail: slick{at}utmb.edu


    Abstract
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 Abstract
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 Technique
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Background. Reperfusion injury remains a significant and sometimes fatal problem in clinical lung transplantation. Controlled reperfusion of the transplanted lung using white cell–filtered, nutrient-enriched blood has been shown recently to significantly ameliorate reperfusion damage in a porcine model. We modified this experimental technique and applied it to human lung transplantation.

Methods. Approximately 1,500 mL of arterial blood was slowly collected in a cardiotomy reservoir during the lung implant, and mixed to make a 4:1 solution of blood:modified Buckberg perfusate. This solution was passed through a leukocyte filter and into the transplant pulmonary artery for 10 minutes, at a controlled rate (200 mL/min) and pressure (less than 20 mm Hg), immediately before removal of the vascular clamp.

Results. Five patients underwent lung transplantation (1 bilateral, 4 single lung) using this technique. All patients were ventilated on a 40% fraction of inspired oxygen within a few hours and extubated on or before the first postoperative day.

Conclusions. Controlled reperfusion of the transplanted lung with white cell–filtered, nutrient-enriched blood has given excellent functional results in our small initial clinical series.


    Introduction
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 Abstract
 Introduction
 Technique
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Reperfusion injury remains a significant problem in clinical lung transplantation, with 10% to 20% of transplanted lungs severely affected [1]. Recently, Halldorsson and coworkers [2, 3] demonstrated near complete amelioration of lung reperfusion injury in porcine models of in situ warm ischemia and 24-hour cold storage single-lung transplant using 10 minutes of controlled reperfusion with nutrient-enriched, white cell–filtered blood. We were impressed with these results and dismayed at the persistent problem of transplant lung reperfusion injury, so we began using their technique with minor modifications. Herein we report our modified technique and results in our first five patients.


    Technique
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Patients were given 10,000 units of heparin intravenously just before native lung pneumonectomy. The bronchial anastomosis was done in the usual manner. Before beginning the pulmonary vascular anastomoses, a -inch arterial drainage catheter was routed to the perfusionist. Arterial access for this line was either through an 8-F cardioplegia cannula (Medtronic DLP Inc, Grand Rapids, MI) placed in a convenient spot in the aorta (descending aorta in left lung transplant and ascending aorta for double lung transplant) or through a 5-F percutaneous femoral artery cannula. The perfusion circuit consisted of a conventional cardiotomy reservoir with 1,500 units of heparin, a conventional blood cardioplegia administration set, a roller pump, and a Pall BC1B leukocyte reduction filter (Pall Corp, Glen Cove, NY).

While the pulmonary venous and arterial anastomoses were constructed, approximately 1,500 mL of blood was slowly allowed to fill the reservoir. The perfusionist controlled inflow from the patient by intermittently clamping and unclamping the drainage line; during this time, the anesthesiologist gave the patient an appropriate volume of blood or colloid to replace the loss. Once the vascular anastomoses were completed (but left untied), the modified (Table 1) Buckberg blood perfusate (Central Admixture Pharmacy Services Inc, Houston, TX) (4 parts blood: 1 part crystalloid solution) was delivered to the operating field at 37°C into a retrograde coronary sinus catheter (model 94615; Medtronic DLP, Inc), which was inserted through the untied pulmonary artery anastomosis, and the anastomotic suture was snared (Fig 1). The warm blood reperfusion solution was then delivered at approximately 200 mL/min, and the flow was adjusted to keep pulmonary artery pressure less than 20 mm Hg, as measured at the tip of the retrograde catheter. The atrial cuff anastomosis was propped open, allowing unimpeded egress of the wash-out into the thorax, which was aspirated into a cell-salvage system. The salvaged and washed red blood cells were returned to anesthesia personnel for later reinfusion. During this time the lung was gently ventilated with 50% inspired oxygen concentration. After 10 minutes of controlled reperfusion, the patient was placed in a head-down position, the retrograde catheter and pulmonary artery clamp were removed, and the pulmonary artery anastomosis was tied. The atrial clamp was then removed, and after air was removed from the graft the atrial anastomosis was tied.


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Table 1. Reperfusion Solution

 


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Fig 1. Reperfusion solution is given with the left atrial clamp in place and the anastomosis propped open, allowing unimpeded egress of wash-out into the chest.

 

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We made some minor modifications to the system proposed by Halldorsson and coworkers [2]. First, unlike their technique, in which the atrial clamp is removed, we left the clamp on the native atrial cuff, diverting effluent into the chest. This is to keep air away from the atrium until air has been removed from the graft and to keep the lung preservation solution and modified Buckberg reperfusion solution out of the systemic circulation, to avoid potential washout-induced hypotension. This effluent goes directly to the cell salvage system, and only the washed red blood cells are returned to the patient. Second, we used a retrograde cardioplegia cannula in the pulmonary artery for ease of pressure measurement. Third, we use a cardiotomy reservoir. This allows us to begin withdrawing blood several minutes before reperfusion, thus spreading the shift in intravascular volume over time.

We have developed this technique in five patients (two with left lung transplants for idiopathic pulmonary fibrosis, one with bilateral lung transplant for cystic fibrosis, and two with left lung transplants for chronic obstructive pulmonary disease, all off cardiopulmonary bypass). During the bilateral lung transplant, significant hypotension and a brief period of cardiac arrest occurred after reperfusion of the first lung. In retrospect, that could have been caused by hypovolemia combined with an undetected air embolus from the pulmonary venous cuff. The patient, a 30-year-old man with cystic fibrosis, had transient inferior ST-segment elevation and a creatinine kinase-MB peak of 24.7 ng/mL. His postoperative cardiac function, however, was excellent. We have no reason to suspect that air could have gotten into the ascending aorta from the aortic cannula, but in the future we might use the descending aorta or femoral artery via percutaneous access to eliminate this possibility.

During reperfusion, our first two patients became hypotensive because of hypovolemia. Despite the low priming volume of the circuit, we found it difficult to keep up with the rate of blood loss using simultaneous intravenous infusion. Thus, we modified our protocol by adding a cardiotomy reservoir and initiating blood removal with mL/mL replacement using 6% hetastarch solution or packed red blood cells several minutes before reperfusion; we have been pleased with the resultant hemodynamic stability.

Although we have not yet used this technique in a transplant done on cardiopulmonary bypass, we plan to do so when the opportunity arises.

The technique undoubtedly increases the likelihood of blood transfusion. In patients with marginal initial hematocrit level, we immediately use intravenous packed red blood cell transfusion while filling the cardiotomy reservoir. These five patients required a total of 15 units of packed red blood cells within the first 24 hours from the beginning of the operation (including 5 units to the bilateral lung recipient and 7 units to a single lung recipient who returned to the operating room 3 hours after implant for repair of a leaking left atrial anastomosis). However, we think that the gains in early graft function have outweighed any transfusion risks.

We used conventional lung procurement methods. Dilute PGE-1 was injected into the pulmonary artery immediately before cardiac arrest, followed by 4 L of University of Wisconsin solution flush, with a bag height of less than 1 m. Venting was done through a generous left atrial appendage opening. Two lungs (one before our use of controlled reperfusion, and one from this series) were harvested for us by outside teams, using Eurocollins solution but otherwise the same technique.

All 5 patients have had excellent function of their transplanted lungs. They were ventilated on 40% inspired oxygen concentration within a few hours and were extubated on or before the first postoperative day. By historical comparison, we performed six off-bypass lung transplants (four single lung, two bilateral lung) in the 2 years before this series. Two patients had severe reperfusion injury; one survived after a prolonged period of mechanical ventilation, and the other died 1 week postoperatively.

In summary, once the anastomoses are completed, the transplanted lung will need to be perfused with blood. The surgical team has the choice of using uncontrolled, unfiltered blood, as in the conventional technique, or nutrient-enriched, white cell–filtered blood under controlled flow and pressure for the vital first few minutes [4]. We think there is significant experimental evidence that the latter technique is superior. However, proof that such a protocol decreases reperfusion injury in humans will have to await a prospective, randomized trial.


    References
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 Abstract
 Introduction
 Technique
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 References
 

  1. Novick R.J., Gehman K.E., Ali I.S., Lee J. Lung preservation. Ann Thorac Surg 1996;62:302-314.[Abstract/Free Full Text]
  2. Halldorsson A.O., Kronon M., Allen B.S., et al. Controlled reperfusion after lung ischemia. J Thorac Cardiovasc Surg 1998;115:415-425.[Abstract/Free Full Text]
  3. Halldorsson A.O., Kronon M., Allen B.S., et al. Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation. Ann Thorac Surg 1998;66:877-885.[Abstract/Free Full Text]
  4. Bhabra M.S., Hopkinson D.N., Shaw T.E., Hooper T.L. Critical importance of the first 10 minutes of lung graft reperfusion after hypothermic storage. Ann Thorac Surg 1996;61:1631-1635.[Abstract/Free Full Text]
Accepted for publication August 20, 1999.


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This Article
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