Objectives

1. Review the crisis in organ donation.
2. Discuss brain death and physiologic consequences.
3. Describe medical management of the potential organ donor.
4. Review lung donor selection and the use of marginal lung donors.
5. Define specific strategies and approaches to the potential lung donor.

Abbreviations

CVP = central venous pressure; DI = diabetes insipidus; ICP = intracranial pressure; MAP = mean arterial pressure; PAC = pulmonary artery catheter; POD = potential organ donor

Solid organ transplant represents the only available life-saving treatment for patients with end-stage pulmonary, cardiac, or liver disease. Unfortunately, there is a growing shortage of donated organs that severely handicaps transplantation availability. Demand dramatically exceeds supply, as there are currently over 80,000 patients on transplantation waiting lists. This number has grown by 16% per year, while the number of donors has remained stagnant at 5,800 per year.¹ The average wait on the lung transplantation waiting list is over 700 days. Approximately 12% of the patients listed for a lung transplant will die each year, and 40 to 50% of patients identified as suitable transplant candidates will die of their underlying disease before an organ is available. This translates into two deaths on the lung transplant waiting list for every three patients from the waiting list who receive a transplant. Although the national conversion rate of potential organ donors (PODs) to actual donors is 42%,¹ it is crucial to recognize that only approximately 15% of the actual donors become lung donors. It is estimated that 80% of multiple donor procurements do not have at least one lung procured. For example, with a national POD pool of 13,800 people, there will be 5,800 actual donors. However, only 15% (870 people) of the 5,800 actual donors will be lung donors, or 6% of the POD pool. Although the lung is more fragile and frequently compromised in the brain-death event, there is enormous variation in the rates of lung procurement (6.1 to 27%), suggesting that there is substantial opportunity for improvement.

Maximal utilization and optimal management of PODs represent two of the most immediate and practical solutions to the current organ shortage crisis. This approach requires surveillance to identify patients with severe neurologic injury that is likely to progress to brain death, a standardized method for the declaration of brain death, a uniform request for consent, and optimal medical management of the donor from declaration to procurement. The latter mandates continued intensity of treatment support; however, the focus shifts from cerebral protective strategies to maintaining and optimizing the donor organs for transplantation. With the possibility of procuring multiple organs per donor, medical management of that donor is analogous to providing critical care to the organs of multiple patients simultaneously. This management period is of crucial importance for several reasons; first, it facilitates donor somatic survival to ensure that the organ procurement can be undertaken; second, the organs to be procured are maintained in their best possible condition; and third, judicious management of the donor can impact upon the short- and long-term organ functions of the recipient.

Recognizing that approximately 40% of lung donors originate from nontraumatic settings, this review is intended to provide all critical care practitioners an overview of the selection and management of the lung donor. Insofar as the brain-dead donor must somatically survive for the lungs to be procured, the impact of brain-death physiology and donor hemodynamic stabilization will be reviewed, followed by specific discussions of donor lung selection and management.

Brain Death and Pathophysiologic Implications

Brain death is a devastating physiologic process that almost uniformly will precipitate somatic death within 24 to 48 h.² Brain death progressing to somatic death alone or in combination with overwhelming initial injuries is thought to be responsible for the loss of 10 to 25% of PODs.³ As a consequence of this process, the period prior to formal declaration is frequently punctuated by hemodynamic instability, cardiac arrest, electrolyte abnormalities, and disorders of thermoregulation at a minimum. Delays in the formal declaration of brain death or securing consent can compound the proceeding for the POD. A precise understanding of the pathophysiological process of brain death is essential to the best management of the POD.

The process that begins with brain-injury-induced intracranial pressure (ICP) elevation, and culminates in herniation and brain death, is termed coning. From animal models, it appears that coning represents progressive cerebrospinal ischemia that begins in the cerebrum and progresses in a rostrocaudal fashion. Defined levels of brain ischemia produce characteristic physiologic correlates. Ischemia at the pons level superimposes sympathetic stimulation upon vagal activation from cerebral ischemia to produce the classic Cushing response, consisting of hypertension, bradycardia, and irregular breathing. This is an adaptive compensatory measure to maintain cerebral perfusion pressure by increasing mean arterial pressure (MAP) in response to increased ICP (cerebral perfusion pressure=MAP-ICP). Subsequent ischemia of the medulla oblongata inactivates the vagal response resulting in a hypertensive tachycardic response defined as the autonomic storm. In these latter periods, serum catecholamine levels are proportional to the rapidity of the ICP rise and may increase several hundredfold. Subsequent spinal cord ischemia produces sympathetic deactivation, a decrease in serum catecholamine levels to below baseline, vasodilation, and hypotension.⁴ Coincident ischemic damage to the hypothalamus and pituitary results in thermoregulatory and endocrine dysfunction. Posterior pituitary dysfunction with diabetes insipidus (DI) is well established. However, the endocrinopathy of the anterior pituitary remains controversial. Substantial animal and limited human data support a state of hypothalamic-pituitary axis dysfunction dominated by thyroid hormone and cortisol depletion, culminating in significant and progressive organ deterioration.⁵ Low levels of thyroid hormone are proposed to impair mitochondrial function, metabolic substrate utilization, and adenosine triphosphate production. In animal models and limited human series, the transition from aerobic to anaerobic metabolism correlates with organ deterioration and hypotension that is responsive to exogenous hormone replacement. Alternatively, several human series have failed to establish the absolute presence of an endocrinopathy and have been unable to correlate cardiovascular stability, inotropic requirements, and serum lactate measurements with hormone levels, or show a beneficial outcome response to exogenous administration. Reconciling these dichotomous observations may relate to the dual blood supply of the anterior pituitary. The inferior hypophysial artery originates extradurally from the internal carotid and is protected from the effects of the increased ICP and may allow for anterior pituitary perfusion and residual function in some donors.

Brain death is proposed to induce organ dysfunction via an ischemia-reperfusion injury mechanism related to the intense vasoconstriction and low flow associated with the autonomic storm, followed by vasodilatation and reflow. Ischemia-reperfusion injury could also occur with the initial traumatic shock event, after organ procurement, during cold storage, and following transplantation.⁶ Recent studies suggest that brain death promotes systemic inflammatory and immunologic effects that include upregulation of inflammatory cytokines, increased expression of cell adhesion molecules/antigens, and endothelial changes that may contribute to short- and long-term recipient organ dysfunction.⁷

Brain death and its accompanying influence on donor organ quality is increasingly recognized to impact upon outcome after transplantation.⁸ Brain-death-induced upregulation of cytokines and lymphokines, widespread microvascular and endothelial changes, increased expression of cell adhesion molecules, and major histocompatability antigens are proposed to create an immunologic continuum between the donor and recipient.⁷ Significant pulmonary inflammation in organ donors following fatal nontraumatic brain injury has been reported.⁹ In this donor population, open lung biopsy and BAL revealed significant increases in neutrophil concentration, IL-8 and GRO- a levels, and lung IL-8 mRNA. Neutrophil infiltration correlated with BAL IL-8 and GRO- a levels. This suggests that there is preclinical injury to the lung prior to transplantation. In a subsequent study, relating donor inflammation to recipient outcome, the same authors correlated IL-8 expression and neutrophil infiltration in the donor with recipient graft function and survival. IL-8 signal in the donor correlated with the percentage of neutrophils in the donor BAL, degree of impairment of graft oxygenation, development of severe early graft dysfunction, and early recipient mortality.¹⁰ Thus, it appears that there is pre-existing subclinical inflammation in the donor that predisposes the recipient to early dysfunction and an adverse prognosis. Attenuation of the donor inflammatory response prior to retrieval may evolve as a therapeutic approach to improve graft function. In addition to the preceding, poor lung retrieval and graft function have been attributed to an unknown pulmonary history (occupational, infectious, and tobacco), the brain-death causative event (aspiration, pulmonary contusion, shock, resuscitation, and neurogenic pulmonary edema), and the complications of mechanical ventilation (atelectasis, pneumonia, barotrauma/volutrauma, oxygen toxicity, and pulmonary embolism).

Medical Management

Although lung procurement has recently been reported in non-brain-dead heart-beating donors (donation after cardiac death), the overwhelming majority of procured lungs will continue to be derived from brain-dead organ donors in the foreseeable future. This requires somatic survival of the donor until lung procurement. The period surrounding brain death and leading to procurement is frequently punctuated by donor instability. It is estimated that between 8 and 20% of PODs are lost in maintenance prior to procurement. In a series of trauma potential donors, Nygaard and colleagues¹¹ reported cardiovascular instability in 80%, DI in 53 to 93%, disseminated intravascular coagulation in 25%, and cardiopulmonary resuscitation in 25%, resulting in a loss of 8% of potential donors.

A structured and organized approach to donor management is associated with a higher consent rate and fewer medical failures, resulting in more actual donors and quality organs per donor.^12,13 Hemodynamic management of the donor is controversial because there are few, if any, controlled trials, and recommendations are frequently derived from retrospective case series compromised by insufficient focus upon the identification of the adequacy of volume resuscitation. Hypotension consequent to postautonomic vasodilatation and cardiac dysfunction, and/or hypovolemia, is reported in 50 to 90% of donors. Recognizing and repleting multifactorial hypovolemia are crucial, because sustained hypotension is correlated with cardiac arrest and is more common in donors with hypovolemia treated with vasopressors and DI not receiving antidiuretic hormone.¹⁴ Hypovolemia may result from inadequate resuscitation or third spacing after the original injury, intracranial pressure treatment with fluid restriction, mannitol or diuretics, DI, hyperglycemia-induced osmotic diuresis, or a hypothermic cold diuresis. Relative hypovolemia may be present with loss of vasomotor tone secondary to brain death or spinal injury and rewarming of a hypothermic donor.

Competing organ interests may produce antagonistic fluid replacement strategies; a minimally positive fluid balance is associated with higher rates of lung procurement, whereas hydration facilitates renal function. Excessive donor volume resuscitation resulting in progressive inhospital pulmonary dysfunction is speculated to be the single most correctable factor precluding donor lung procurement. Compared to donors from whom lungs were successfully procured, a significantly positive (7000 mL vs 300 mL) fluid balance was seen in potential donors failing to donate lungs.¹⁵ No patient with progressive inhospital pulmonary dysfunction had fluid and vasopressor therapy guided by the use of a pulmonary artery catheter (PAC). Volume resuscitation to achieve a central venous pressure (CVP) of 8 to 10 mm Hg is associated with significant increases in the alveolar-arterial oxygen gradient.¹⁶ Therefore, placement of a PAC should be strongly considered when it is necessary to adjudicate competing organ fluid requirements and optimize vasoactive support. Incorporation of a PAC into donor management protocols has been shown to improve the rate of organ salvage and is recommended for optimizing cardiovascular function when heart and lung donation is a consideration. Optimizing cardiovascular function is thought to enhance all donor organ function. All fluids should be warmed to prevent hypothermia and its consequences. Hypotonic solutions should be used to correct hypernatremia associated with DI, and hydroxyethyl starch should be avoided, because it is reported to induce tubular epithelial injury and may impair early renal graft function.¹⁷

It is estimated that 70 to 90% of donors can be managed successfully with volume resuscitation and low-dose vasopressors. Dopamine has traditionally been the vasopressor of choice and should be initiated to maintain a MAP of 60 mm Hg and a cardiac index ≥ 2.5 L/min. Escalating vasopressor requirements that most likely reflect progressive underlying donor severity of illness have prompted associations between poor recipient outcome and vasopressor use. However, this observation is inconsistent, and weak associations have also been reported. Recently, catecholamines have been reported to exert beneficial immunomodulatory effects leading to less rejection and improved long-term graft survival.¹⁸ Aqueous vasopressin at 0.3 m g/kg/min is a potent vasoconstrictor that can be initiated in vasopressor refractory hypotension. Aqueous vasopressin is proposed to enhance vascular catecholamine sensitivity, which may diminish catecholamine requirements and has been shown to maintain prolonged hemodynamic instability in brain-dead patients. In donors requiring ≥ 10 m g/kg/min of vasopressors, hormonal resuscitation with triiodothyroxine, hydrocortisone, and insulin has been reported to stabilize donors leading to higher rates of procurement. Although hemodynamic stabilization is crucial for donor somatic survival, vigilant attention to cardiac arrhythmias, electrolyte abnormalities, hypothermia, coagulopathy, and hyperglycemia is equally important. Ventilatory issues will be addressed below.

Lung Donor Selection

Traditionally, only ideal donor lungs were procured and transplanted into ideal recipients, given the risks of the procedure. The standard donor criteria listed in Table 1 were developed early in the lung transplant era. These were arbitrarily defined and have not been subjected to rigorous evaluation. Similar to the liberalized criteria for other organs prompted by the organ shortage, most exclusions are becoming absolutely relative and relatively absolute. Given the dire shortage of donor lungs, it has been suggested that the current standard lung donor criteria be challenged by obtaining, analyzing, and using multicenter data from a well-designed database, similar to that which has been undertaken in heart transplantation with the Cardiac Transplant Research Database. Weill¹⁹ has proposed that the classic criteria be ignored, because, although some make intuitive sense, most are quite controversial. For example, criteria for oxygenation and the influence of tracheal donor cultures are derived from the early transplant era and may not be applicable today. Recent reports suggest that there is no relationship between donor Gram stain results and recipient outcomes in the current era of broad-spectrum prophylactic antibiotics. Rigid adherence to the standard criteria, which excludes patients with purulent secretions, will unnecessarily limit the number of lungs procured. Shortcomings of the current standard criteria are also evident at autopsy when examining lungs not procured. In a large series of PODs, from whom no lungs were procured, 47% of donors were defined as suitable lung donors by standard criteria. At autopsy, 40% of these suitable donors manifested significant pulmonary disease, and 25% had bronchopneumonia. Of the 53% that were nonsuitable donors based upon standard criteria, 14% had only minor pulmonary abnormalities.¹⁴ Autopsy examinations of the nontransplanted lungs, from 15 donors deemed suitable and procured for single lung transplant, revealed evidence of emphysema, pulmonary hypertension, hemorrhage, focal pneumonia, and interstitial fibrosis in nine lungs and extensive pulmonary emboli and overinflation in three lungs. Thus, it appears that there is minimal correlation between normal function, chest radiographs, and abnormal histologic findings.²⁰ Similarly, significant bronchoscopic findings that correlated with adverse recipient outcome were found in donors fulfilling the standard criteria for suitability.²¹ Given the shortage of donor lungs and deaths on the lung waiting list, there is an evolving trend to breech the standard criteria and utilize what have traditionally been described as marginal lungs. Recipient outcomes with marginal donor lungs are reported to be comparable to ideal donor lungs. Figure 1 depicts the reported series and the specific variables used to compare outcomes of marginal and ideal lungs. These studies are discussed below.

Marginal Lung Studies

Kron and Colleagues, 1993²²

In this prospective study, the authors personally inspected marginal donor organs that previously would have been rejected by standard donor criteria. A total of 10 of the 11 marginal lungs that were inspected were transplanted, and nine did well postoperatively. This expanded the donor pool by 36%. Marginal lungs were defined by a Pao₂ ≤ 350 mm Hg on 100% Fio₂, the presence of infiltrates on the chest radiograph, or purulent secretions on bronchoscopy. Marginal lungs were acceptable if the patient had been ventilated ≤ 48 h and the secretions were easily cleared by suctioning. A Gram stain revealing bacteria did not exclude a donor unless there was gross fungal contamination. Antibiotics based upon the donor Gram stain were initiated in the recipient. Aggressive ventilatory and fluid management was also utilized.

Shumway and Colleagues, 1994²³

This series liberalized the donor criteria to accept donors up to 60 years old and included donors with any kind of smoking history, unless there was a documented history of chronic obstructive lung disease or pulmonary fibrosis on chest radiograph. Donors with Gram-negative rods in the sputum were accepted and treated with antibiotics, although, those with fungus were excluded. A Pao₂ ≥ 100 mm Hg on 40% Fio₂ was required, and donors were accepted with small pulmonary infiltrates. Fluid restriction, ventilatory recruitment, and gentle suctioning were used to limit atelectasis and improve oxygenation.

Sundaresan and Colleagues, 1995²⁴

In this study of 133 consecutive lung transplants, 44 donors were considered marginal because of age ≥ 55, a smoking history of ≥ 20 pack-years, an unsatisfactory chest radiograph, or a Pao₂ ≤ 300 mm Hg on an Fio₂ of 1.0. Compared to recipients receiving ideal lungs, recipients receiving marginal lungs showed no difference in median duration of postoperative mechanical ventilation, alveolar-arterial gradient immediately posttransplant, and status at 24 hours or mortality.

Gabbay and Colleagues, 1999²⁵

The Australian organ allocation system allows for the identification of marginal donors, when appropriate. This study compared the impact of utilization of marginal donors and aggressive donor management. Donor management included antibiotic therapy, strict fluid management, bronchoscopy, and bronchial toilet and alteration of ventilatory settings. Maximizing organ utilization was facilitated by the transplant respiratory physician maintaining contact with the donor hospital intensivist, personal inspection of the donor whenever possible, and reassessment of blood gas values after therapeutic manipulations. Figure 2 depicts the flow of patients in the study based upon Pao₂ /Fio₂ ratios. A total of 29% (59 patients) of donors initially had an unacceptable Pao₂ /Fio₂ ≤ 300 mm Hg. After excluding 18 patients who were clearly unsuitable, aggressive donor management was initiated in the remainder of the donors with a marginal Pao₂ /Fio₂ ratio. Approximately 50% of those marginal donors (20 of 41) were able to achieve a Pao₂ /Fio₂ ≥ 300 mm Hg and were successfully transplanted. Thus, aggressive donor lung management was able to achieve an acceptable Pao₂ /Fio₂ ≥ 300 mm Hg in donors who were initially deemed unsuitable. In this study, 57% of lung transplants were done with marginal lungs. Similar outcomes between ideal and marginal lungs were reported in postoperative gas exchange, ICU length-of-stay, and short- or medium-term mortality.

Bhorade and Colleagues, 2000²⁶

Extended donors in this series differed from ideal donors by age ≥ 55 years, tobacco history ≥ 20 pack-years, the presence of infiltrates on chest radiograph, donor ventilator time ≥ 5 days, and use of inhaled drugs. No significant differences between the two groups were found with respect to operating room complications (cardiopulmonary bypass, bleeding complications, and life-threatening arrhythmias) or ICU complications (pneumonia, airway dehiscence, and reoperation within 30 days related to transplant). Intubation times, hospital length-of-stay, hospital survival, 1-year follow-up, pulmonary function, and survival were similar and without significant difference. It should be recognized that all donors in this study had a Pao₂ /Fio₂ ≥ 350 mm Hg or an Fio₂ of 1.0.

Straznicka and Colleagues, 2002²⁷

This retrospective review focused upon 27 of 194 donors who were initially deemed unacceptable for lung transplantation by standard protocol. After aggressive donor management, consisting of invasive monitoring, methylprednisolone, fluid restriction, inotropic agents, bronchoscopy, and diuresis, the Pao₂ /Fio₂ ratios, CVPs, fluid balances, dopamine requirements, and chest radiographs of initially unacceptable donors were comparable to those of acceptable donors. There were no differences in mortality between groups at 30 days or 1 year.

Pierre and Colleagues, 2002²⁸

In this retrospective review of 128 consecutive lung or heart-lung transplants, donors were considered extended when age was ≥ 55 years, smoking was ≥ 20 pack-years, infiltrates were present on chest radiograph, the Pao₂ was < 300 mm Hg, or purulent secretions were visualized on bronchoscopy. Overall, 51% of donors were considered extended. This is the first study to report a higher 30-day mortality in recipients from extended donors (17.5% vs 6.2%) compared to ideal donors. Subgroup analysis revealed that the highest mortality was in the nonguideline recipients who received lungs from extended donors. The cause of death in 6 of the 11 recipients who died and received extended donor lungs was believed to be possibly related to the quality of donor lungs. Although the majority of extended lungs functioned adequately, the authors cautioned against using extended donor lungs with bilateral infiltrates or truly purulent secretions in nonguideline recipients, as this combination seemed to have the highest risk of death.

From the reported literature, it appears that recipient outcomes from marginal or extended donors are comparable to outcomes from ideal donors for the vast majority of recipients. However, it is important to weigh the character of the available marginal/extended donor lung against the character and status of the proposed recipient. Further investigation is needed to develop indices to quantify/qualify the degree of donor-lung injury, identify reversible causes of dysfunction, and further define interventions to successfully modify lungs deemed initially unacceptable.

Management Strategies and Approaches

General ICU Management

Consensus recommendations for the general ICU management are presented in Table 2. All patients should have a bronchoscopy performed to inspect the airway and obtain cultures. Frequent suctioning and pulmonary toilet are important to minimize aspirations, mucus pooling with resultant atelectasis, and gas exchange impairment. After brain death, P co 2 should be allowed to normalize, which will decrease the minute ventilation mitigating against hyperventilation-induced shear injury and potential barotrauma. Recruitment maneuvers and positive end-expiratory pressure should be judiciously applied to minimize atelectasis and optimize gas exchange. No donor should be excluded based upon an initial, arterial blood gas reading. Bronchoscopy, pulmonary hygiene, ventilatory manipulations, and fluid management should be undertaken in an attempt to achieve the best Pao₂ with the least positive end-expiratory pressure before a final decision is made regarding donor suitability. Fluid balance assessment should require CVP measurements at a minimum and placement of a PAC when fluid balance needs to be more precisely defined.

Aggressive Organ Procurement Organization Management

Lung Management

Focused efforts targeted at increasing the number of procured lungs have reported substantial success. Cummings and colleagues²⁹ reported a 201% increase in the rate of successful lung procurement from 15.8 to 31.8% of PODs. This was accomplished by educational initiatives and revisions in the donor management protocols. Classroom didactic sessions overviewing general principles of donor management and lung-specific topics were incorporated into the organ recovery coordinator's orientation. Radiologic findings and the relevance to donor management decisions were reviewed, along with detailed discussions of fluid resuscitation, ventilatory management, and aggressive pulmonary toilet. Coordinators also followed the donor to the operating room, participated in the bronchoscopy, and reviewed the case with the transplant surgeon. Management protocols were modified to maximize ventilatory support by increasing the tidal volume from 10 to 15 mL/Kg, increasing the frequency of suctioning from 2-h to 1-h intervals and targeting a central venous pressure (CVP) of 6 to 8 mm Hg rather than the traditional 10 to 12 mm Hg. The increase in successful procurement was attributed to a decline in the number of lungs lost to pulmonary edema with accompanying unacceptable blood gas results and a decline in the lungs lost to abnormal intraoperative bronchoscopic findings. Judicious fluid management and aggressive pulmonary toilet were proposed to be responsible for the declines, respectively.²⁹ Similarly, in a retrospective review, Straznicka and colleagues²⁷ were able to show that after aggressive organ procurement organization management, Pao₂ /Fio₂ ratios (103 to 463 mm Hg), CVPs (11.3 to 6.7 mm Hg), dopamine requirements (15 to 5.2 m g/kg/min), and the incidence of radiographic abnormalities (77 to 0%) of initially unacceptable donors were comparable to those of acceptable donors. The preceding was accomplished by utilizing invasive monitoring to adjust inotropes and fluid balance, resulting in net 1.7-L negative fluid balance. All patients underwent bronchoscopy and received methylprednisolone.

Multidisciplinary Management

Consensus agreement among solid organ transplant groups, regarding donor management and the development of multidisciplinary algorithms for donor management, has been shown to dramatically increase the rate of lung procurement. With this approach, Follette and colleagues³⁰ reported that the initiation of a local lung transplant program was able to increase the lung procurement rate from 1.2 to 28% of PODs. Importantly, there was no adverse effect upon the other solid organs, as the number of organs procured per donor increased from 2.7 to 3. The management strategies employed consisted of early bronchoscopy, ventilatory management, invasive hemodynamic monitoring with an emphasis upon colloid, and early treatment with steroids and thyroxine. Early access to, and continuous involvement with, a transplant pulmonologist was felt to be crucial to the management success.

Fluid Balance

A significantly positive fluid balance is thought to be the most reversible cause of progressive pulmonary dysfunction that precludes lung procurement. Virtually all of the successful initiatives targeting increased donor lung procurement have incorporated invasive monitoring to either limit or optimize fluid balance. Reilly and colleagues¹⁵ reported only a positive 300 mL fluid balance in successfully procured lungs compared to a positive balance of 7,000 mL in donors from whom lungs were not procured. In a randomized trial of potential donors with CVP ≤ 6 mm Hg, 3.7 L of crystalloid, over 90 min, was required to achieve a CVP of 8 to 10 mm Hg. This was associated with a significant increase in the Pao₂ /Fio₂ ratio. Lowering of the CVP was associated with an improvement in the Pao₂ /Fio₂ ratio but never to the original baseline. Interestingly, the pulmonary capillary wedge pressure was consistently higher than the CVP, leading to speculation that measuring CVP alone is inadequate.¹⁶

Steroids

Brain death with absent cerebral blood flow has been proposed to produce the endocrinopathy of brain-death manifested with low-circulating levels of glucocorticoids and thyroid hormone. Although contentious, hormonal rescue has been incorporated into many donor management protocols. In conjunction with the brain-death-induced donor lung inflammation, the use of steroids is appealing. Retrospectively, methylprednisolone administered at 14.5 mg/kg has been shown to improve the Pao₂ /Fio₂ ratio and was associated with an increased rate of lung procurement.³¹

Unilateral Lung Dysfunction

Potential lung donors are frequently deemed unacceptable because standard criteria do not differentiate between unilateral and bilateral disease. Many adequate single lungs are not utilized as a result of isolated contralateral disease. Puskas and colleagues³² reported intraoperative unilateral ventilation and perfusion to assess single-lung function in potential donors with contralateral disease. In each case, donor arterial oxygen was initially below the acceptable limits (mean 246 mm Hg). But, after clamping the pulmonary artery to the injured lung and selectively ventilating the uninjured lung, the arterial oxygen tension was excellent (mean 499 mm Hg), and the unilateral lung was successfully procured and transplanted. Therefore, donors with clearly unilateral evidence of pulmonary dysfunction should be assessed for procurement and not deemed unacceptable based upon the initial arterial oxygen tension.

Conclusion

References

1. Sheehy E, Conrad SL, Brigham LE, et al. Estimating the number of potential organ donors in the United States. N Engl J Med 2003; 349:667-674
2. Black PM. Brain death (first of two parts). N Engl J Med 1978; 299:338-344
3. Lopez-Navidad A, Domingo P, Viedma MA. Professional characteristics of the transplant coordinator. Transplant Proc 1997; 29:1607-1613
4. Shivalkar B, Van Loon J, Wieland W, et al. Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function. Circulation 1993; 87:230-239
5. Novitzky D. Donor management: state of the art. Transplant Proc 1997; 29:3773-3775
6. Tilney NL, Paz D, Ames J, et al. Ischemia-reperfusion injury. Transplant Proc 2001; 33:843-844
7. Gasser M, Waaga AM, Laskowski IA, et al. Organ Transplantation from brain-dead donors: its impact on short and long term outcome revisited. Transplantation Rev 2001; 15:1-10
8. Pratschke J, Wilhelm MJ, Kusaka M, et al. Brain death and its influence on donor organ quality and outcome after transplantation. Transplantation 1999; 67:343-348
9. Fisher AJ, Donnelly SC, Hirani N, et al. Enhanced pulmonary inflammation in organ donors following fatal non-traumatic brain injury. Lancet 1999; 353:1412-1413
10. Fisher AJ, Donnelly SC, Hirani N, et al. Elevated levels of interleukin-8 in donor lungs is associated with early craft failure after lung transplantation. Am J Respir Crit Care Med 2001; 163:259-265
11. Nygaard CE, Townsend RN, Diamond DL. Organ donor management and organ outcome: a 6-year review from a level I trauma center. J Trauma 1990; 30:728-732
12. Jenkins DH, Reilly PM, Schwab CW. Improving the approach to organ donation: a review. World J Surg 1999; 23:644-649
13. Rosendale JD, Chabalewski FL, McBride MA, et al. Increased transplanted organs from the use of a standardized donor management protocol. Am J Transplantation 2002; 2:761-768
14. Finfer S, Bohn D, Colpitts D, et al. Intensive care management of pediatric organ donors and its effect on post-transplant organ function. Intensive Care Med 1996; 22:1424-1432
15. Reilly PM, Grossman MD, Rosengard, et al. Lung procurement from solid organ donors: role of fluid resuscitation in procurement failures. Chest 1996; 110 (suppl): 222S
16. Pennefather SH, Bullock RE, Dark JH. The effect of fluid therapy on alveolar arterial oxygen gradient in brain-dead organ donors. Transplantation 1993; 56:1418-1422
17. Cittanova ML, Leblanc I, Legendre C, et al. Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients. Lancet 1996; 348:1620-1622
18. Schnuelle P, Berger S, de Boer J, et al. Effects of catecholamine application to brain-dead donors on graft survival in solid organ transplantation. Transplantation 2001; 72:455-463
19. Weill D. Donor criteria in lung transplantation: an issue revisited. Chest 2002; 121:2029-2031
20. Husain AN, Hinkamp TJ. Donor lung pathology: correlation with outcome of transplanted contralateral lung. J Heart Lung Transplant 1993; 12(6 Pt 1):932-939
21. Riou B, Guesde R, Jacquens Y, et al. Fiberoptic bronchoscopy in brain-dead organ donors. Am J Respir Crit Care Med 1994; 150:558-560
22. Kron IL, Tribble CG, Kern JA, et al. Successful transplantation of marginally acceptable thoracic organs. Ann Surg 1993; 217:518-522
23. Shumway SJ, Hertz MI, Petty MG, et al. Liberalization of donor criteria in lung and heart-lung transplantation. Ann Thorac Surg 1994; 57:92-95
24. Sundaresan S, Semenkovich J, Ochoa L, et al. Successful outcome of lung transplantation is not compromised by the use of marginal donor lungs. J Thorac Cardiovasc Surg 1995; 109:1075-1079
25. Gabbay E, Williams TJ, Griffiths AP, et al. Maximizing the utilization of donor organs offered for lung transplantation. Am J Respir Crit Care Med 1999; 160:265-271
26. Bhorade SM, Vigneswaran W, McCabe MA, et al. Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation. J Heart Lung Transplant 2000; 19:1199-1204
27. Straznicka M, Follette DM, Eisner MD, et al. Aggressive management of lung donors classified as unacceptable: excellent recipient survival one year after transplantation. J Thorac Cardiovasc Surg 2002; 124:250-258
28. Pierre AF, Sekine Y, Hutcheon MA, et al. Marginal donor lungs: a reassessment. J Thorac Cardiovasc Surg 2002; 123:421-427
29. Cummings J, Houck J, Lichtenfeld D. Positive Effect of Aggressive Resuscitative Efforts on Cadaver Lung Procurement. J Transplant Coordination 1995; 5:103-106
30. Follette D, Rudich S, Bonacci C, et al. Importance of an aggressive multidisciplinary management approach to optimize lung donor procurement. Transplant Proc 1999; 31:169-170
31. Follette DM, Rudich SM, Babcock WD. Improved oxygenation and increased lung donor recovery with high-dose steroid administration after brain death. J Heart Lung Transplant 1998; 17:423-429
32. Puskas JD, Winton TL, Miller JD, et al. Unilateral donor lung dysfunction does not preclude successful contralateral single lung transplantation. J Thorac Cardiovasc Surg 1992; 103:1015-1017