C u r ren t R e s e a rc h o n O r g a n D o n o r Management Mitchell Sally,
MD,
Darren Malinoski,
MD*
KEYWORDS Organ donor management Organ donation Graft outcomes Transplantation Donor management goals KEY POINTS A shortage of organs is available for transplantation, and therefore improving the critical care provided to potential donors may increase the quantity and quality of the organs. A brief summary of the existing organ donor management literature is discussed and descriptions of ongoing studies are presented. Standardizing donor management practices through the use of bundles/checklists has the potential to improve outcomes and provide a framework for future, randomized studies.
INTRODUCTION
A shortage of organs is available for transplantation, with 116,000 patients on the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) wait list.1 Because the demand for organs outweighs the supply, considerable care must be taken to maximize the number of organs transplanted per donor and optimize the quality of the organs recovered. Studies designed to determine optimal donor management therapies are limited, and this research has many challenges.2 Although evidenced-based guidelines for managing potential organ donors do not exist, research in this area is increasing. This article reviews the existing literature and highlights some recent trials that can guide management. Neurologic death is accompanied by myriad immunologic, hemodynamic, and endocrine abnormalities.3 This article focuses on management of the cardiovascular, pulmonary, renal, hepatic, pancreatic, endocrine, and coagulation organ systems in potential donors after neurologic determination of death (DNDDs) in the intensive care unit (ICU) and the operating room.
Portland VA Medical Center, Oregon Health & Science University, PO Box 1034/Mail Code P3ANES, Portland, OR 97207, USA * Corresponding author. E-mail address: [email protected] Anesthesiology Clin 31 (2013) 737–748 http://dx.doi.org/10.1016/j.anclin.2013.08.004 1932-2275/13/$ – see front matter Published by Elsevier Inc.
anesthesiology.theclinics.com
738
Sally & Malinoski
CARDIOVASCULAR SYSTEM
Up to 34% of potential DNDDs can experience cardiovascular collapse, and aggressive critical care management is needed to avoid the loss of organs from these donors.4 Echocardiography is routinely used to assess the left ventricular function of a potential donor heart. Cardiac catheterization may be more selectively used for donors older than 55 years and younger patients with a history of cocaine use, or those with 3 or more risk factors for coronary artery disease, such as hypertension, diabetes, dyslipidemia, prolonged smoking history, or family history of premature coronary artery disease.5 In the setting of left ventricular dysfunction, pulmonary artery catheter-directed management can maximize donor recovery. Properly managed younger hearts with left ventricular dysfunction have been shown to markedly recover function after transplantation.6 At minimum, all DNDDs should have either central venous pressure (CVP) guidance or other fluid responsiveness monitors for resuscitation and support. If a pulmonary artery catheter is used, it is designed to optimize cardiac output and maintain normal preload and afterload. The role of adjunctive hormone therapy to improve cardiac function is discussed later. In up to 90% of donors, endogenous vasopressin is noted to be either absent or low7 and, in donors requiring catecholamine support, is often inadequate to maintain homeostasis.8 In a retrospective study by Plurad and colleagues,9 the use of arginine vasopressin in the DNDD was associated with more organs transplanted per donor. Additional agents, such as dopamine, phenylephrine, or norepinephrine, may be titrated as needed to maximize end-organ perfusion. Echocardiogram changes and cardiac arrhythmias are common in DNDDs and are thought to be caused by both metabolic and electrolyte abnormalities and infarction of the conduction system. The use of standard antiarrhythmic therapy is appropriate. An important caveat is that vagus nerve disruption in the brain stem may result in a bradyarrhythmia, which is resistant to the effects of atropine, and therefore a b-adrenergic agonist, such as isoproterenol or epinephrine, may be required.10 Untreated arrhythmias may become completely refractory to management if not treated early and aggressively. PULMONARY SYSTEM
Standard criteria for lung donation stipulate that suitable donors must have a ratio of PaO2 to fraction of inspired oxygen (FIO2) greater than 300 mm Hg (PaO2 >300 mm Hg with 100% FIO2 on 5 cm H2O positive end-expiratory pressure [PEEP]). The origins of this threshold are unclear and likely based on conjecture rather than observation. Although most centers follow this guideline in selecting donors, limited but conflicting experience with donors who deviate from this standard has occurred. In a multicenter French retrospective review of transplants performed between 1988 and 1998, donor PaO2:FIO2 less than 350 mm Hg was associated with a steep increase in the risk of death.11 In contrast, Luckraz and colleagues12 retrospectively reviewed 362 donor and recipient pairs over a 17-year period and found no difference in 1- and 5-year survivals for recipients with donor PaO2:FIO2 less than 300 mm Hg compared with greater than 300 mm Hg. Reyes and colleagues13 analyzed the UNOS database containing more than 10,000 primary transplants in the United States and found that donor PaO2:FIO2 was less than 300 mm Hg in 18% of cases (n 5 1751 recipients), and survival to 7 years for this group was similar to that of recipients in whom donor PaO2:FIO2 exceeded 300 mm Hg. Tailored lung donor management protocols involving diuresis, therapeutic bronchoscopy, chest physiotherapy, and lung recruitment maneuvers have been shown
Current Research on Organ Donor Management
to improve oxygenation parameters in donors who initially fail to meet the standard oxygenation requirement. In a study from Australia, an aggressive lung donor protocol led to achievement of a PaO2:FIO2 greater than 300 mm Hg in 20 of 59 potential donors whose initial oxygenation was less than this threshold.14 A similar strategy, including use of a recruitment maneuver of pressure-controlled ventilation at an inspiratory pressure of 25 cm H2O and PEEP of 15 cm H2O for 2 hours, was used by the San Antonio lung transplant program. Of 98 donors, one-third converted from unacceptable to acceptable PaO2:FIO2 ratios in response to this protocol.15 Traditionally, donor management protocols used by organ procurement organizations (OPOs) recommend using tidal volumes of 10 to 15 mL/kg when ventilating potential lung donors. A recent multicenter randomized trial examined a lung-protective ventilatory strategy similar to that used in patients with acute respiratory distress syndrome.16 Potential donors were randomized to 1 of 2 strategies: a conventional protocol using tidal volumes of 10 to 12 mL/kg, 3 to 5 cm PEEP, and an open circuit for both suctioning and apnea tests; or a lung-protective protocol using tidal volumes of 6 to 8 mL/kg, 8 to 10 cm PEEP, a closed circuit for suctioning, continuous positive airway pressure equal to previous PEEP for apnea tests, and recruitment maneuvers after any disconnection from the ventilator. Use of the lung-protective protocol doubled lung recovery rates (54% vs 27%; P
MD,
Darren Malinoski,
MD*
KEYWORDS Organ donor management Organ donation Graft outcomes Transplantation Donor management goals KEY POINTS A shortage of organs is available for transplantation, and therefore improving the critical care provided to potential donors may increase the quantity and quality of the organs. A brief summary of the existing organ donor management literature is discussed and descriptions of ongoing studies are presented. Standardizing donor management practices through the use of bundles/checklists has the potential to improve outcomes and provide a framework for future, randomized studies.
INTRODUCTION
A shortage of organs is available for transplantation, with 116,000 patients on the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) wait list.1 Because the demand for organs outweighs the supply, considerable care must be taken to maximize the number of organs transplanted per donor and optimize the quality of the organs recovered. Studies designed to determine optimal donor management therapies are limited, and this research has many challenges.2 Although evidenced-based guidelines for managing potential organ donors do not exist, research in this area is increasing. This article reviews the existing literature and highlights some recent trials that can guide management. Neurologic death is accompanied by myriad immunologic, hemodynamic, and endocrine abnormalities.3 This article focuses on management of the cardiovascular, pulmonary, renal, hepatic, pancreatic, endocrine, and coagulation organ systems in potential donors after neurologic determination of death (DNDDs) in the intensive care unit (ICU) and the operating room.
Portland VA Medical Center, Oregon Health & Science University, PO Box 1034/Mail Code P3ANES, Portland, OR 97207, USA * Corresponding author. E-mail address: [email protected] Anesthesiology Clin 31 (2013) 737–748 http://dx.doi.org/10.1016/j.anclin.2013.08.004 1932-2275/13/$ – see front matter Published by Elsevier Inc.
anesthesiology.theclinics.com
738
Sally & Malinoski
CARDIOVASCULAR SYSTEM
Up to 34% of potential DNDDs can experience cardiovascular collapse, and aggressive critical care management is needed to avoid the loss of organs from these donors.4 Echocardiography is routinely used to assess the left ventricular function of a potential donor heart. Cardiac catheterization may be more selectively used for donors older than 55 years and younger patients with a history of cocaine use, or those with 3 or more risk factors for coronary artery disease, such as hypertension, diabetes, dyslipidemia, prolonged smoking history, or family history of premature coronary artery disease.5 In the setting of left ventricular dysfunction, pulmonary artery catheter-directed management can maximize donor recovery. Properly managed younger hearts with left ventricular dysfunction have been shown to markedly recover function after transplantation.6 At minimum, all DNDDs should have either central venous pressure (CVP) guidance or other fluid responsiveness monitors for resuscitation and support. If a pulmonary artery catheter is used, it is designed to optimize cardiac output and maintain normal preload and afterload. The role of adjunctive hormone therapy to improve cardiac function is discussed later. In up to 90% of donors, endogenous vasopressin is noted to be either absent or low7 and, in donors requiring catecholamine support, is often inadequate to maintain homeostasis.8 In a retrospective study by Plurad and colleagues,9 the use of arginine vasopressin in the DNDD was associated with more organs transplanted per donor. Additional agents, such as dopamine, phenylephrine, or norepinephrine, may be titrated as needed to maximize end-organ perfusion. Echocardiogram changes and cardiac arrhythmias are common in DNDDs and are thought to be caused by both metabolic and electrolyte abnormalities and infarction of the conduction system. The use of standard antiarrhythmic therapy is appropriate. An important caveat is that vagus nerve disruption in the brain stem may result in a bradyarrhythmia, which is resistant to the effects of atropine, and therefore a b-adrenergic agonist, such as isoproterenol or epinephrine, may be required.10 Untreated arrhythmias may become completely refractory to management if not treated early and aggressively. PULMONARY SYSTEM
Standard criteria for lung donation stipulate that suitable donors must have a ratio of PaO2 to fraction of inspired oxygen (FIO2) greater than 300 mm Hg (PaO2 >300 mm Hg with 100% FIO2 on 5 cm H2O positive end-expiratory pressure [PEEP]). The origins of this threshold are unclear and likely based on conjecture rather than observation. Although most centers follow this guideline in selecting donors, limited but conflicting experience with donors who deviate from this standard has occurred. In a multicenter French retrospective review of transplants performed between 1988 and 1998, donor PaO2:FIO2 less than 350 mm Hg was associated with a steep increase in the risk of death.11 In contrast, Luckraz and colleagues12 retrospectively reviewed 362 donor and recipient pairs over a 17-year period and found no difference in 1- and 5-year survivals for recipients with donor PaO2:FIO2 less than 300 mm Hg compared with greater than 300 mm Hg. Reyes and colleagues13 analyzed the UNOS database containing more than 10,000 primary transplants in the United States and found that donor PaO2:FIO2 was less than 300 mm Hg in 18% of cases (n 5 1751 recipients), and survival to 7 years for this group was similar to that of recipients in whom donor PaO2:FIO2 exceeded 300 mm Hg. Tailored lung donor management protocols involving diuresis, therapeutic bronchoscopy, chest physiotherapy, and lung recruitment maneuvers have been shown
Current Research on Organ Donor Management
to improve oxygenation parameters in donors who initially fail to meet the standard oxygenation requirement. In a study from Australia, an aggressive lung donor protocol led to achievement of a PaO2:FIO2 greater than 300 mm Hg in 20 of 59 potential donors whose initial oxygenation was less than this threshold.14 A similar strategy, including use of a recruitment maneuver of pressure-controlled ventilation at an inspiratory pressure of 25 cm H2O and PEEP of 15 cm H2O for 2 hours, was used by the San Antonio lung transplant program. Of 98 donors, one-third converted from unacceptable to acceptable PaO2:FIO2 ratios in response to this protocol.15 Traditionally, donor management protocols used by organ procurement organizations (OPOs) recommend using tidal volumes of 10 to 15 mL/kg when ventilating potential lung donors. A recent multicenter randomized trial examined a lung-protective ventilatory strategy similar to that used in patients with acute respiratory distress syndrome.16 Potential donors were randomized to 1 of 2 strategies: a conventional protocol using tidal volumes of 10 to 12 mL/kg, 3 to 5 cm PEEP, and an open circuit for both suctioning and apnea tests; or a lung-protective protocol using tidal volumes of 6 to 8 mL/kg, 8 to 10 cm PEEP, a closed circuit for suctioning, continuous positive airway pressure equal to previous PEEP for apnea tests, and recruitment maneuvers after any disconnection from the ventilator. Use of the lung-protective protocol doubled lung recovery rates (54% vs 27%; P
