Organ donation in adults: a critical care perspective

More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP. In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital. During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP. Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059.).

While the adoption of practice guidelines is standardizing many aspects of patient care, ethical dilemmas are occurring because of forgoing life-sustaining therapies in intensive care and are dealt with in diverse ways between different countries and cultures. To determine the frequency and types of actual end-of-life practices in European intensive care units (ICUs) and to analyze the similarities and differences. A prospective, observational study of European ICUs. Consecutive patients who died or had any limitation of therapy. Prospectively defined end-of-life practices in 37 ICUs in 17 European countries were studied from January 1, 1999, to June 30, 2000. Comparison and analysis of the frequencies and patterns of end-of-life care by geographic regions and different patients and professionals. Of 31 417 patients admitted to ICUs, 4248 patients (13.5%) died or had a limitation of life-sustaining therapy. Of these, 3086 patients (72.6%) had limitations of treatments (10% of admissions). Substantial intercountry variability was found in the limitations and the manner of dying: unsuccessful cardiopulmonary resuscitation in 20% (range, 5%-48%), brain death in 8% (range, 0%-15%), withholding therapy in 38% (range, 16%-70%), withdrawing therapy in 33% (range, 5%-69%), and active shortening of the dying process in 2% (range, 0%-19%). Shortening of the dying process was reported in 7 countries. Doses of opioids and benzodiazepines reported for shortening of the dying process were in the same range as those used for symptom relief in previous studies. Limitation of therapy vs continuation of life-sustaining therapy was associated with patient age, acute and chronic diagnoses, number of days in ICU, region, and religion (P<.001). The limiting of life-sustaining treatment in European ICUs is common and variable. Limitations were associated with patient age, diagnoses, ICU stay, and geographic and religious factors. Although shortening of the dying process is rare, clarity between withdrawing therapies and shortening of the dying process and between therapies intended to relieve pain and suffering and those intended to shorten the dying process may be lacking.

The inhibition of cellular metabolism induced by hypothermia obviates the possibility of substantial reparative processes occurring during organ preservation. The aim of this study was to develop a technique of extended (12-hour) ex vivo lung perfusion (EVLP) at normothermia for assessment and protective maintenance of the donor lung. Six double-lung blocks from 35-kg pigs and 5 single human lungs were subjected to 12 hours of normothermic EVLP using acellular Steen Solution. In the animal studies, the left lung was transplanted into recipients at the end of EVLP and reperfused for 4 hours to evaluate the impact of prolonged EVLP on post-transplant lung function. A protective mode of mechanical ventilation with controlled perfusion flows and pressures in the pulmonary vasculature were employed during EVLP. Lung oxygenation capacity (DeltaPo(2)), pulmonary vascular resistance and airway pressures were evaluated in the system. Red blood cells were added to the perfusate to a hematocrit of 20% at the end of human lung EVLP to study lung functional assessment with and without cells. Lung function was stable during 12 hours of EVLP. This stability during prolonged normothermic EVLP translated into excellent post-transplant lung function (Pao(2)/Fio(2): 527 +/- 22 mm Hg), low edema formation (wet/dry ratio: 5.24 +/- 0.38) and preserved lung histology after transplantation. The acellular perfusion assessment of lung function accurately correlated with post-transplant graft function. Twelve hours of EVLP at physiologic temperatures using an acellular perfusate is achievable and maintains the donor lungs without inflicting significant added injury. This system can be used to assess, maintain and treat injured donor lungs.