Surgery News - October 2008 - (Page 10)

TRANSPLANT lower DGF rate (2 [8%] of 24) than did kidneys from DBD donors (24 [24%] of 100). The protocol resulted in a 24% increase in the overall number of deceased donor kidneys ( J. Trauma 2005;58:10951102). Dr. Bartlett and his colleagues are switching from perfusing the donor at body temperature to room temperature. Dr. Hines and his colleagues are submitting a paper that describes their experience with a series of patients with severe and unrecoverable neurologic injury (but without brain death) who underwent the center’s extracorporeal interval support for organ retrieval (EISOR) protocol. The group has now transplanted kidneys, pancreases, and livers from these DCD donors by using the EISOR circuit and protocol, designed by Dr. Hines and Dave Charles, chief perfusionist at Wake Forest. In this protocol, organs are slowly cooled in situ to 20°-25° C to ensure that their metabolic processes are inactive when they are procured and flushed with a cold saline solution. This mimics the process of deep hypothermic circulatory arrest that is achieved when cardiopulmonary bypass machines cool a patient’s blood until the oxygen demand of organs and tissue is nearly zero. The cooling process might account for why kidneys from EISOR donors have a lower DGF rate than do organs from DBD donors, which are rapidly cooled from normo thermic to hypothermic temperatures during procurement, Dr. Hines said. The technique also may have the effect of mimicking ischemic preconditioning, in which the arterial blood supply to an organ such as the liver is cut off briefly in order to prepare the organ to withstand the stress of a longer period of ischemia that will follow, he explained. All the pancreases procured by the Wake Forest team with the EISOR protocol have functioned immediately and survived in the recipient. SURGERY NEWS • O C T O B E R 2 0 0 8 Adding to Pool Donor Organs • from page 1 extracorporeal membrane oxygenation (ECMO) service. Only Wake Forest and the University of Michigan, Ann Arbor, have substantial experience in using extracorporeally supported DCD protocols after the withdrawal of life support, but Dr. Hines noted that similar services are getting underway at other hospitals. After consent for donation has been granted, the common protocol for extracorporeally supported DCD in severely neurologically impaired patients begins with preparatory cannulation of the femoral artery and vein in the ICU. Organ procurement does not proceed unless cardiac death occurs within 60 minutes of withdrawal of life support. Once the primary medical team declares death, another 5 minutes must pass to ensure that cardiac reanimation does not occur. The primary medical team is separated from the organ procurement service at all steps. Dr. Robert H. Bartlett, the inventor of ECMO, and his colleagues at the University of Michigan have refined their extracorporeal support protocol to include the use of an aortic occlusion balloon catheter to block blood from returning to the heart. Dr. Bartlett, an ACS Fellow, and Dr. Hines said in interviews that thus far, all of the families given the option of the extracorporeal technique for organ donation “have been cooperative, supportive, very positive about it [and] frequently bring it up when discussing the withdrawal of care,” Dr. Hines said. Michigan researchers, who were the first to perform extracorporeal support of DCD donors, reported delayed graft function in 2 (11%) of 19 transplanted kidneys (Ann. Transplant. 2004;9:57-8). Later, they found that kidneys taken from extracorporeally supported DCD donors had a “That’s a pretty good sign that this technique works,” Dr. Hines said. The setup for the procedure involves the percutaneous insertion of cannulae into a femoral artery and vein of the donor. These cannulae are attached to a “simplified and very portable heart-lung machine” with a single centrifugal Well-perfused organs are shown in this procedure using the pump, an oxygena- extracorporeal interval support for organ retrieval protocol. tor, and a heat exThe Department of Health and Huchanger, he said. With greater understanding of organ man Services has funded a pilot project at preservation techniques, Dr. Hines sus- New York’s Bellevue Hospital that seeks to pects that the arbitrary 1-hour window in determine the feasibility of procuring orwhich the heart must stop beating in or- gans from people who die from sudden der for organ procurement to proceed cardiac death. The protocol, which is not could change to a system in which the po- yet established, would allow paramedics tential donor is monitored for as long as who work around the hospital to call a second group of paramedics with a specially stable physiologic signs are present. “To be ultraconservative [in pronounc- outfitted ambulance to begin extracorpoing death], we wait for 5 minutes after real support in people who are unsucelectrical silence of the heart rather than cessfully resuscitated. The process for consent and the possifor 5 minutes after pulselessness,” Dr. Hines said. After that, lidocaine is mixed bility of placing cannulae prior to consent into the perfused blood to prevent reani- are issues that are still under debate. But no organs would be procured without mation of the heart during the process. At both centers, the local organ pro- consent of family, according to Dr. curement organizations have paid the ex- Bartlett, who has consulted with Bellevue tra costs entailed by extracorporeal sup- on the project. The unknown, yet unlikely, potential to port, but providing better-functioning donor organs could offset those costs by resuscitate the brain of these potential reducing the number of days donor organ DCD donors with extracorporeal support recipients spend in the ICU. Both groups would be prevented with an aortic occluhave used their protocols only on patients sion balloon, Dr. Bartlett said. Already at some centers, cardiac arrest with severe, irreversible neurologic injury. But a much larger organ donor pool exists patients who are unsuccessfully resuscifor “uncontrolled” organ donation from tated on ECMO can become DCD donors with their family’s consent. people who have sudden cardiac death. ■ Trial Supports Early Steroid Withdrawal After Renal Transplant recipients and their physicians remained blinded as to assigned treatment for the full 5-year study duration. The primary composite end point in the trial was death, N E W YO R K — Withdrawal of corticosteroids 7 days af- graft loss, or severe acute rejection. The rate for this end ter kidney transplantation results in patient and allograft point was similar—roughly 15%—in the early steroid survival rates comparable to those achieved with chron- withdrawal and chronic steroid maintenance arms. Fracture or avascular necrosis occurred in ic steroid maintenance therapy, while avoiding 5.2% of the early withdrawal patients, versus the myriad adverse cardiovascular, bone, and 11.3% of those on chronic steroids. There were metabolic consequences of long-term steroids, no deaths due to infection in the early withaccording to a 5-year, double-blind, placebodrawal group, versus 3.1% in the chronic maincontrolled, randomized trial. tenance group. Serum triglyceride levels were These results counter those of a 25-year-old a mean of 50 mg/dL lower in the early withCanadian randomized trial that concluded that drawal group for the first 4 years of follow-up. early steroid withdrawal significantly increased There was also less new-onset diabetes in the risk of graft failure. That study has served the early withdrawal group: Insulin therapy as a major obstacle to widespread adoption of early removal of steroids, Dr. E. Steve Woodle, The composite end for 30 days or more was required in only 3.7% an ACS Fellow, reported at the annual meet- point of death, graft of the early withdrawal group but in 11.6% of patients on chronic steroids. ing of the American Surgical Association. loss, or severe On the other hand, the early withdrawal “We believe that the primary difference with acute rejection was group had a higher rate of chronic allograft the Canadian trial is their patients were on roughly 15% in nephropathy: 9.9%, versus 4.1% in the chronSandimmune (cyclosporine) monotherapy with both trial arms. ic steroid group. But this was not associated inadequate trough levels. This is very different DR. WOODLE with any differences in renal function. from being on tacrolimus and mycophenolate Of note, the average prednisone dose in the control mofetil, modern potent immunosuppression,” said Dr. Woodle, professor of surgery and director of the division group was only 5 mg/day after 6 months. Had higher maintenance doses of prednisone been used, as often ocof transplantation at the University of Cincinnati. He presented the final results of the 34-center trial, in curs in clinical practice, the advantages of early steroid which the 386 participating adult kidney transplant withdrawal would have been even greater, Dr. Woodle said. BY BRUCE JANCIN Else vier Global Medical Ne ws A key procedural point was that steroid withdrawal at 1 week post transplant was always carried out with T-cell depleting antibody induction using Thymoglobulin (rabbit antithymocyte globulin) or interleukin-2R antibody. Dr. Woodle said he believes this is the right way to go, citing a University of Cincinnati study that showed a 40% reduction in the risk of acute rejection with the use of T-cell depleting antibody induction. Overall, 20% of the study participants were African American, a group known to be at high risk for graft rejection. They had no increase in graft failure with early steroid withdrawal, and experienced greater cardiovascular risk reduction with early withdrawal than other groups. Mortality in African Americans with a functioning graft was only 4% in those withdrawn from steroids early, versus 16% in those with chronic steroids. Discussant Dr. Ron Shapiro, an ACS Fellow, c

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Surgery News - October 2008

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