EXPERIMENTAL AND CLINICAL TRANSPLANTATION

A brain-dead donor experienced repeated cardiac arrests followed by severe hypotension requiring multiple vasoactive agents. These events were associated with severe lactic acidosis and dysregulated kidney function in the donor. A 10-hour treatment with extracorporeal membranous oxygenation was instituted, which was able to hemodynamically stabilize the donor. This treatment protocol resulted in the procurement of 2 viable kidney grafts transplanted into 2 recipients, who had immediate kidney graft function and excellent serum creatinine levels upon hospital discharge. These results are all the more significant considering that both cases involved long cold ischemia times, and one of the recipients had diabetes and was receiving his second kidney graft.

Key words : Cold ischemia time, ECMO, Hemodynamics, Renal transplantation, Tissue and organ procurement

The shortage of available organs is a major problem in the field of transplantation. Brain-dead donors—the largest source of potential organs—often show hemodynamic instability owing to loss of central control, leading to cardiac arrest and possibly failure of organ procurement. These potential donors need optimized therapeutic support to prevent donor loss and increase the number of viable retrieved organs.^1,2

Extracorporeal membranous oxygenation (ECMO) has been increasingly used as bridge therapy for patients with potentially reversible cardiac or respiratory failure. Normally, patients offered this form of treatment are deemed to have good overall organ status before experiencing acute cardiac or respiratory events.³

In patients in whom ECMO is used to treat cardiac or respiratory failure, the results are encouraging. However, a significant number of patients treated with ECMO do not recover because of either the nonsalvageable nature of their heart or respiratory condition or a neurologic event that sometimes accompanies this form of therapy.^1-3

There have been few reports about the outcomes of organs retrieved from patients after treatment with ECMO. Orandi and colleagues (2015) reported that, out of 82 143 deceased-donor kidney transplants, 22 185 (27.0%) recipients developed delayed graft function (DGF).⁴ In contrast, Carter and colleagues reported on 29 recipients of standard kidney grafts from brain-dead donors who had received ECMO treatment and who were documented over a 17-year period at Thomas Jefferson University, Philadelphia. In these recipients, the prevalence of DGF was 34.0%.⁵ This rate was also higher than those reported in a large number of recipients of deceased-donor kidneys from 177 centers using Scientific Registry of Transplant Recipients data (median, 27.3%; interquartile range, 18.7%-33.8%), although it was not statistically significant.⁴ Carter and colleagues also reported that the discard rate of kidneys procured following ECMO treatment was 25%. In the group of patients who received these organs, 1-year graft survival was reported as 93%.⁵

There have been even fewer reports of ECMO used not with therapeutic intent, but to support and maintain the patient’s organs for transplant if brain death, cardiac arrest, or circulatory collapse takes place before organ retrieval can occur.^6,7 One such study⁷ reported on 4 donors treated with ECMO for 9.5 to 78.0 hours before their death. Two of the 8 kidneys could not be used (discard rate, 25%), and the other 6 were successfully transplanted (DGF rate, 33%). In 2 donors, ECMO was started because of circulatory collapse and in the other 2 donors because of noticeable deterioration of liver or kidney function. In all patients, ECMO treatment resulted in significant improvement in blood pressure (BP), reduced need for vasoactive agents, and significant drops in levels of serum creatinine, bilirubin, and alanine transaminase (ALT).

This report presents the case of a brain-dead potential donor with hemodynamic instability despite maximal medical support. After declaration of brain death, the potential donor was supported with ECMO therapy to perfuse his organs until their procurement.

A 44-year-old man with known hypertension was admitted to the emergency department in a deep coma (Glasgow Coma Scale, 3/15) and was intubated to secure the airway. A computed tomography brain scan revealed massive right intracerebral hemorrhage with midline shift and brain herniation.

Initial investigations revealed serum creatinine of 0.89 mg/dL, blood urea nitrogen 12 mg/dL, ALT 44 U/L, AST 25 U/L, bilirubin 1.1 mg/dL, sodium 139 mEq/L, and potassium 2.7 mEq/L. After 12 hours of stabilization and correction of significant electrolyte instability, brain death was confirmed using Saudi Center for Organ Transplantation guidelines.

Twenty-four hours later, the potential donor became unstable without evidence of concomitant sepsis, despite aggressive medical management with maximal dosages of vasopressor support comprising norepinephrine (2 mg/kg/min) and epinephrine (2 mg/kg/min). His BP was 80/40 mm Hg at best, and he showed signs of severe hypoperfusion, skin mottling and peripheral cyanosis, decreased urine output (< 0.5 mL/kg/h), and severe lactic acidosis (lactate, 12 mmol/L). Laboratory testing showed serum creatinine of 1.07 mg/dL, blood urea nitrogen 18 mg/dL, lactate 12 mmol/L, sodium 164 mEq/L, and potassium 2 mEq/L despite correction (Table 1).

The option of ECMO implantation was discussed, and we decided to start ECMO as a bridge to organ donation, after obtaining organ donation consent from his family.

Meanwhile, in the emergency room, he displayed severe ventricular arrhythmias in the form of ventricular fibrillation refractory to conventional cardiopulmonary resuscitation and advanced life support given for 10 minutes. Immediately, using ultrasound guidance, the left femoral artery was cannulated using a 19F, 23-cm arterial cannula, while the right femoral vein was cannulated with a 25F, 55-cm venous multistage cannula. Cannulation took only 7 minutes, and femoro-femoral venoarterial ECMO immediately commenced, with a starting flow of 3.5 L/min, rising to 4.2 L/min (CARDIOHELP System; Maquet, Rastatt, Germany). Although the patient’s heart continued in ventricular fibrillation, his BP rose to 64/34 mm Hg, the skin of the upper half of his body looked perfused, mottling disappeared, and lactic acidosis improved, decreasing from a pH of 12 to 8 and then to 4.

As cardiopulmonary resuscitation continued, the patient received a bolus of potassium ≤ 120 mEq and 6 g magnesium sulfate, as his potassium concentration was 0.7 mmol/L measured by arterial blood gas analysis. After 1 hour of cardiopulmonary resuscitation, cardioversion, and ECMO support, the heart started to beat again. The patient was then transferred to the intensive care unit for invasive hemodynamic monitoring and prepared for organ retrieval.

While in the intensive care unit, he remained mostly in ventricular fibrillation despite being given megadoses of potassium chloride ≤ 240 mEq, amiodarone, and repeated direct-current shocks. An ECMO flow of 3.7 to 4.5 L/min maintained nonpulsatile BP of 54/37 mm Hg and provided tissue perfusion, which decreased and maintained serum lactate at ~4 mmol/L and urine output at > 0.5 mL/kg/min.

Laboratory findings 5 hours after ECMO support began showing creatinine of 2.3 mg/dL, blood urea nitrogen 27 mg/dL, ALT 34 U/L, AST 74 U/L, total bilirubin 0.9 mg/dL, sodium 17 mEq/L, potassium 2 mEq/L, and lactate 3.5 mmol/L.

The procedures for organ retrieval were performed under ECMO support for a total of 3 hours. The cold ischemia times for each kidney were 22 hours and 14 hours.

Table 2 shows the characteristics of the 2 kidney recipients, aged 42 and 45 years. One recipient had diabetes and was receiving his second graft. The grafts functioned immediately in both recipients, whose discharge serum creatinine levels were 147 μmol/L and 97 μmol/L.

The annual registry report of the Saudi Center for Organ Transplantation for 2015 shows that, of the 27 unrecovered kidneys from confirmed and consenting donors who later experienced brain death, 16 (67%) were unusable owing to circulatory collapse (sudden cardiac arrest). Had the hospitals been able to use these kidneys, the number of kidney transplants from deceased donors performed in Saudi Arabia in 2015 would have risen by 19%: from 86 to 102.⁸ Similar trends have been noted in Saudi Center for Organ Transplantation registry reports for the previous 12 years. Similarly, one center report from the United States in which ECMO was used to enable organ donation after cardiac death significantly increased the number of kidneys transplanted by 24%.⁹

Our report shows that, despite repeated cardiac arrests in the donor with low BP requiring multiple vasoactive agents, severe lactic acidosis, and dysregulated kidney function, a 10-hour treatment with ECMO managed to stabilize him and resulted in 2 viable grafts. These were transplanted into 2 recipients with immediate kidney function and excellent discharge serum creatinine levels.

The potential of ECMO to substantially expand the donor pool appears great when used in brain-dead donors whose organs would otherwise be unusable due to circulatory collapse or cardiac arrest. This is important in view of the devastating global shortage of organs for transplant.^10-12 In brain-dead donors, ECMO has been shown not only to preserve the organs until they are retrieved but also to improve the donor’s deteriorating kidney and liver function.⁷

Extracorporeal membranous oxygenation not only gave us time to retrieve the organs but also improved the patient’s hemodynamic status and kidney function and reduced his serum lactate level. It is notable that the patient had comorbid chronic hypertension.

Given all of these factors, graft recipients would be expected to be susceptible to developing DGF. This did not happen in either of them, even though cold ischemia times were prolonged in both patients, and one recipient had diabetes and was receiving his second kidney transplant.

Extracorporeal membranous oxygenation may have a protective effect on kidney tissue. Its mechanisms of action may include protection against damage by oxygen free radicals¹³ or reperfusion injury.¹⁴ Alternatively, ECMO may reduce the severity of the subsequent innate immune response in the recipient, which stimulates the immunologic and inflammatory cascade and initiates a powerful response that can lead to graft rejection.¹⁵

With these possibilities in mind, ECMO could play a future role in reducing the incidence of DGF in cases where it is expected (eg, those with anticipated long cold ischemia times) as well as improving prognosis in expanded-criteria donor kidneys. We propose these as areas of future research.

Volume: 17 Issue: 3 June 2019

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