Leif Pierre

Transplantation of lungs from a non-heart-beating donor

BACKGROUND In animals, we have previously done successful lung transplantations using organs from non-heart-beating donors. We have also developed an ex-vivo system of assessing the function of such organs before transplantation. The next stage was to try the technique in human beings. Bearing in mind the sensitive ethical issues involved, our first aim was to find out what procedures would be acceptable, and to use the results to guide a clinical lung transplantation from a non-heart-beating donor. METHODS The ethical acceptability of the study was gauged from the results of a broad information programme directed at the general public in Sweden, and from discussions with professionals including doctors, nurses, hospital chaplains, and judges. The donor was a patient dying of acute myocardial infarction in a cardiac intensive-care unit after failed cardiopulmonary resuscitation. The next of kin gave permission to cool the lungs within the intact body, and intrapleural cooling was started 65 min after death. Blood samples were sent for virological testing and cross matching. The next of kin then had time to be alone with the deceased. After 3 h, the body was transported to the operating theatre and the heart-lung block removed. The lungs were assessed ex vivo, and the body was transported to the pathology department for necropsy. RESULTS No contraindications to transplantation were found, and the right lung was transplanted successfully into a 54-year-old woman with chronic obstructive pulmonary disease. The donor lung showed excellent function only 5 min after reperfusion and ventilation, and during the first 5 months of follow-up, the function of the transplanted lung has been good. INTERPRETATION About half the deaths in Sweden are caused by cardiac and cerebrovascular disease. This group could be a potential source of lung donors. When all hospitals and ambulance personnel in Sweden have received training in non-heart-beating lung donation, we hope that there will be enough donor lungs of good quality for all patients needing a lung transplant.

The critical importance of minimal delay between chest compressions and subsequent defibrillation: a haemodynamic explanation

Outcome after prehospital defibrillation remains dire. The aim of the present study was to elucidate the pathophysiology of cardiac arrest and to suggest ways to improve outcome. Ventricular fibrillation (VF) was induced in air-ventilated pigs, after which ventilation was withdrawn. After 6.5 min of VF, ventilation with 100% oxygen was initiated. In six pigs (group I), defibrillation was the only treatment carried out. In another six pigs (group II), mechanical chest compression-decompression CPR (mCPR) was carried out for 3.5 min followed by a 40-s hands-off period before defibrillation. If unsuccessful, mCPR was resumed for a further 30 s before a second or a third, 40-s delayed, shock was given. In a final six pigs (group III) mCPR was applied for 3.5 min after which up to three shocks (if needed) were given during on-going mCPR. Return of spontaneous circulation (ROSC) occurred in none of the pigs in group I (0%), in 1 of six pigs in group II (17%) and in five of six pigs in group III (83%). During the first 3 min of VF arterial blood was transported to the venous circulation, with the consequence that the left ventricle emptied and the right ventricle became greatly distended. It took 2 min of mCPR to establish an adequate coronary perfusion pressure, which was lost when the mCPR was interrupted. During 30 s of mCPR coronary perfusion pressure was negative, but a carotid flow of about 25% of basal value was obtained. In this pig model, VF caused venous congestion, an empty left heart, and a greatly distended right heart within 3 min. Adequate heart massage before and during defibrillation greatly improved the likelihood of return of spontaneous circulation (ROSC).

Evaluation of LUCAS, a new device for automatic mechanical compression and active decompression resuscitation.

LUCAS is a new gas-driven CPR device providing automatic chest compression and active decompression. In an artificial thorax model, superior pressure and flow were obtained with LUCAS compared with manual CPR. In a randomized study on pigs with induced ventricular fibrillation significantly higher cardiac output, carotid artery blood flow, end-tidal CO(2), intrathoracic decompression-phase aortic- and coronary perfusion pressures were obtained with LUCAS-CPR (83% ROSC) compared to manual CPR (0% ROSC). In normothermic fibrillating pigs, the ROSC rate was 100% after 15 min and 38% after 60 min of LUCAS-CPR (no drug treatment). The ROSC rate increased to 75% if surface cooling to 34 degrees C was applied during the first 30 min of the 1-h resuscitation period. Experience with the first 20 patients has shown that LUCAS is light (6.5 kg), easy to handle, quick to apply (10-20 s), maintains a correct position, and works optimally during transport both on stretchers and in ambulances. In one hospital patient with a witnessed asystole where manual CPR failed, LUCAS-CPR achieved ROSC within 3 min. One year later the patients mental capacity was fully intact. To conclude, LUCAS-CPR gives significantly better circulation during ventricular fibrillation than manual CPR.

Transplantation of lungs from non–heart-beating donors after functional assessment ex vivo

BACKGROUND If lungs from patients dying of heart attacks are to serve as donor organs in a safe way, their function should be properly assessed before transplantation. The aim of this study was to investigate donor lung function evaluation in a realistic large animal model. METHODS Twelve 60-kg pigs were used. Five minutes after ventricular fibrillation was induced, cardiopulmonary resuscitation was initiated and maintained for 20 minutes. After a 10-min hands-off period, heparin was administered through a central venous catheter followed by 20 chest compressions. Intrapleural cooling was initiated after 65 minutes of warm ischemia. Cooling proceeded for 6 hours within the cadaver, after which lung function was assessed ex vivo. Recipient pigs underwent left lung transplantation followed by right pneumonectomy, thus making these animals 100% dependent for their survival on the function of the donor lungs. RESULTS The assessment showed that all lungs had adequate function to serve as donor lungs. All recipient animals were in good condition during the 24-hour observation period after the operation. The blood gas function did not differ significantly from that in the healthy donor animals before induction of ventricular fibrillation; pulmonary vascular resistance was within normal range. CONCLUSIONS Lungs from non-heart-beating donors topically cooled in situ for 6 hours after 65 minutes of warm ischemia were assessed ex vivo and found to have normal function. They were then transplanted and retained normal function during a 24-hour observation period.

Clinical transplantation of initially rejected donor lungs after reconditioning ex vivo.

BACKGROUND A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. A method to evaluate and recondition lungs ex vivo has been tested on donor lungs that have been rejected for transplantation. METHODS The donor lungs were reconditioned ex vivo in an extracorporeal membrane oxygenation (ECMO) circuit with STEEN solution (Vitrolife AB, Kungsbacka, Sweden) mixed with erythrocytes. The hyperoncotic solution dehydrates edematous lung tissue. Functional evaluations were performed with deoxygenated perfusate by varying the inspired fraction of oxygen. After the reconditioning, the lungs were kept immersed at 8 degrees C in extracorporeal membrane oxygenation until transplantation was performed. RESULTS Six of nine initially rejected donor lungs were reconditioned to acceptable function, and in six recipients, double lung transplantation was performed. Three-month survival was 100%. One patient has since died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are alive and well without any sign of bronchiolitis obliterans syndrome 24 months after the transplantation. CONCLUSIONS The result from the present study is promising, and we continue to transplant reconditioned lungs.

How to Recondition Ex Vivo Initially Rejected Donor Lungs for Clinical Transplantation: Clinical Experience from Lund University Hospital

A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. We have recently reported the results of the first six double lung transplantations performed with donor lungs reconditioned ex vivo that had been deemed unsuitable for transplantation by the Scandiatransplant, Eurotransplant, and UK Transplant organizations because the arterial oxygen pressure was less than 40 kPa. The three-month survival of patients undergoing transplant with these lungs was 100%. One patient died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are still alive and well 24 months after transplantation, with no signs of bronchiolitis obliterans syndrome. The donor lungs were reconditioned ex vivo in an extracorporeal membrane oxygenation circuit using STEEN solution mixed with erythrocytes, to dehydrate edematous lung tissue. Functional evaluation was performed with deoxygenated perfusate at different inspired fractions of oxygen. The arterial oxygen pressure was significantly improved in this model. This ex vivo evaluation model is thus a valuable addition to the armamentarium in increasing the number of acceptable lungs in a donor population with inferior arterial oxygen pressure values, thereby, increasing the lung donor pool for transplantation. In the following paper we present our clinical experience from the first six patients in the world. We also present the technique we used in detail with flowchart.

Clinical experience with a novel endotoxin adsorbtion device in patients undergoing cardiac surgery.

Endotoxaemia is thought to occur in cardiac surgery using extracorporeal circulation (ECC) and a positive correlation has been proposed between the magnitude of endotoxaemia and risk for postoperative complications. We studied the effects of a new endotoxin adsorber device (Alteco® LPS adsorber) in patients undergoing cardiac surgery with ECC, with special reference to safety and ease of use. Fifteen patients undergoing coronary artery bypass and/or valvular surgery were studied. In 9 patients, the LPS Adsorber was included in the bypass circuit between the arterial filter and the venous reservoir. Flow through the adsorber was started when the aorta was clamped and stopped at the end of perfusion. Flow rate was kept at 150 ml/min. Six patients served as controls with no adsorber in the circuit. Samples were taken for analysis of endotoxin, TNFα, IL-1ß and IL-6 as well as complement factors C3, C4 and C1q. Whole blood coagulation status was evaluated using thromboelastograpy (TEG) and platelet count. No adverse events were encountered when the adsorber was used in the circuit. Blood flow through the device was easily monitored and kept at the desired level. Platelet count decreased in both groups during surgery. TEG data revealed a decrease in whole blood clot strength in the control group while it was preserved in the adsorber group. Endotoxin was detected in only 2 patients and IL-1ß in 4 patients. IL-6 decreased in both groups whereas no change in TNF concentrations was found. C3 fell in both groups, but no changes wer found in C4 and C1q. The Alteco® LPS adsorber can be used safely and is easy to handle in the bypass circuit. No complications related to the use of the adsorber were noted. The intended effects of the adsorber, i.e. removal of endotoxin from the blood stream could not be evaluated in this study, presumably due to the small number of patients and the relatively short perfusion times.

Comparison of the effectiveness and safety of a new de-airing technique with a standardized carbon dioxide insufflation technique in open left heart surgery: A randomized clinical trial.

OBJECTIVE We have compared the effectiveness, time required for de-airing, and safety of a newly developed de-airing technique for open left heart surgery (Lund technique) with a standardized carbon dioxide insufflation technique. METHODS Twenty patients undergoing elective open aortic valve surgery were randomized prospectively to the Lund technique (Lund group, n = 10) or the carbon dioxide insufflation technique (carbon dioxide group, n = 10). Both groups were monitored intraoperatively during de-airing and for 10 minutes after weaning from cardiopulmonary bypass by transesophageal echocardiography and online transcranial Doppler for the severity and the number of gas emboli, respectively. The systemic arterial partial pressure of carbon dioxide and pH were also monitored in both groups before, during, and after cardiopulmonary bypass. RESULTS The severity of gas emboli observed on transesophageal echocardiography and the number of microembolic signals recorded by transcranial Doppler were significantly lower in the Lund group during the de-airing procedure (P = .00634) and in the first 10 minutes after weaning from cardiopulmonary bypass (P = .000377). Furthermore, the de-airing time was significantly shorter in the Lund group (9 vs 15 minutes, P = .001). The arterial pH during the cooling phase of cardiopulmonary bypass was significantly lower in the carbon dioxide group (P = .00351), corresponding to significantly higher arterial partial pressure of carbon dioxide (P = .005196) despite significantly higher gas flows (P = .0398) in the oxygenator throughout the entire period of cardiopulmonary bypass. CONCLUSIONS The Lund de-airing technique is safer, simpler, and more effective compared with the carbon dioxide insufflation technique. The technique is also more cost-effective because the de-airing time is shorter and no extra expenses are incurred.

Is it possible to further improve the function of pulmonary grafts by extending the duration of lung reconditioning using ex vivo lung perfusion

Background: The method of ex vivo lung perfusion (EVLP) has been suggested as a reliable means of differentiating between “good” and “poor” pulmonary grafts in marginal donors as, when grafts identified as good by this method are transplanted, the results do not differ from those using lungs fulfilling standard criteria. The EVLP method is also thought to improve pulmonary grafts by reducing lung edema and eliminating lung atelectasis. In the present study, we investigated whether the pulmonary graft could be further improved by extending the duration of EVLP. Methods and Materials: Six Landrace pigs were used. The lungs were reconditioned and evaluated, using the EVLP method, as double lungs. After the initial evaluation, EVLP was continued for a further 90 minutes. Results: The arterial oxygen level (pO2) was 60.8 ± 4.8 kPa after the standard 60 minutes of EVLP and 67.1 ± 2.2 kPa after 150 minutes (p = 0.48). The pulmonary vascular resistance was 453 ± 78 dyne*s/cm5 after 60, 90, 120 and 150 minutes of EVLP (p = 1.0). The pulmonary artery pressure was 17.8 ± 1.0 mmHg after 60, 90, 120, and 150 minutes of EVLP (p = 1.0) and the pulmonary artery flow was 3.5 ± 0.4 l/min after 60, 90, 120, and 150 minutes of EVLP (p = 1.0). The mean weight of the pulmonary grafts after harvesting was 574 ± 20 g at the beginning of EVLP 541 ± 24 g and, after 150 min of EVLP, 668 ± 33 (p = 0.011). Conclusions: The blood gases and hemodynamic parameters in the pulmonary grafts did not improve as a result of the extra 90 minutes of EVLP. However, the weight of the pulmonary graft increased significantly with increasing duration of EVLP, indicating lung perfusion injury.

A randomized study of coronary artery bypass surgery performed with the Resting Heart™ System utilizing a low vs a standard dosage of heparin

OBJECTIVES Allogeneic blood transfusion and reoperation for postoperative bleeding after the coronary artery bypass grafting have a negative impact on the patient outcome. This study aimed at evaluating the effects of reduced doses of heparin and protamine on the patient outcome, using a heparin-coated mini-cardiopulmonary bypass (CPB) system. METHODS Sixty patients undergoing elective first-time CPB were prospectively randomized either to have a reduced systemic heparinization [activated clotting time (ACT) = 250 s] or to a control group perfused with a full heparin dose (ACT = 420 s). Blood transfusions, ventilation time, early postoperative bleeding, ICU stay, reoperations for bleeding, postoperative cognitive status and the level of mobilization were registered. RESULTS Twenty-nine patients were randomized to the control group, 27 patients to the low-dose group and 4 patients were excluded because of protocol violations. Four patients in the control group received a total of 10 units of packed red blood cells, and in the low-dose group, no transfusions were given, P = 0.046. No patient was reoperated because of bleeding. The ICU stay was significantly shorter in the low-dose group (8.4 vs 13.7 h, P = 0.020), less dependent on oxygen on the first postoperative day (78 vs 97%, P = 0.034), better mobilized (89 vs 59%, P = 0.006) and had less pain (visual analogue scale 2.0 vs 3.5, P = 0.019) compared with the control group. CONCLUSIONS The use of a mini-CPB system combined with a low dose of heparin reduced the need for blood transfusions and may facilitate the faster mobilization of the patients.