Organ donation after cardiac death

By Anne Krueger, BSN, CPTC, hospital development coordinator, Wisconsin Donor Network

Organ donation involves a dynamic, sometimes dramatic process with lifesaving results. Currently, there are more than 95,000 people waiting for an organ transplant, and about 3 percent of those are children. More than 26,000 life-saving transplants occurred in 2006, but sadly, 18 people die every day while waiting for a transplant.

Hospital staff works closely with the organ procurement organization (OPO) to offer the opportunity for organ donation to families and to coordinate the donation process. There are 58 OPOs nationally and the Wisconsin Donor Network (WDN) is the OPO designated for Southeastern Wisconsin. Donation begins with an initial referral call from the hospital to the WDN to screen for organ donation potential. Organs can be recovered from a patient who has been declared brain dead or who is eligible for donation after cardiac death (DCD).

The discussion with the family about their donation opportunities should occur once final brain death has been declared or when the decision to withdraw support has been made. The WDN has highly experienced and trained staff to support families at this time and to engage in the request for donation at the hospital. Upon the final consent from the family for donation, the process to fulfill those family or patient wishes begins.

In the case of brain death, it may take 12 to 24 hours to completely evaluate all organs, including, heart, lungs, liver, kidneys, pancreas and intestines. There are many tests and expertise from medical disciplines that determine transplant suitability for each organ. Cardiologists and pulmonologists are vital to perform and interpret echocardiograms, heart catherizations, bronchoscopies and other tests and procedures. When a home is found for all suitable organs, we will proceed to the operating room for the recovery.

DCD may occur when a patient on life support with no chance of recovery is withdrawn from mechanical support and death occurs. With appropriate consent and planning, organs can be recovered immediately after cardiac arrest. In the case of DCD, the process may take six to 12 hours. During this time, we are primarily evaluating the liver and kidneys for transplant. The family determines the time when life support is withdrawn. Most often, the withdrawal of care occurs in the ICU with the family at the bedside. The declaring physician, who is unrelated to transplant, will be present to initiate the DNR order, withdrawal of supports and comfort care measures. At the time of initial pulselessness, the patient is moved to the operating room after the family has a moment to say their final goodbye. Five minutes must pass from initial pulselessness to the pronouncement of death. At this point the patient will be entering the operating room and organ recovery may begin.

The WDN's mission is to "Serve the family." WDN staff tries to ensure that all families are offered the option of donation and to work collaboratively with the hospital staff, maximizing that precious gift of life our families and patients so generously give. We hope to be a resource for all medical disciplines and families when opportunities arise, and we are available 24 hours a day to answer questions.

A research study: Erythropoietin and pediatric cardiac surgery

By Mary Krolikowski, RN, MSN, research coordinator, Herma Heart Center; with Steve Zangwill, MD, assistant professor, Pediatric Cardiology, Medical College of Wisconsin; and John Baker, PhD, professor, Cardiothoracic Surgery, Medical College of Wisconsin

Protection of the infant heart and brain from ischemic injury during surgical repair of congenital heart defects remains a challenge for the cardiac surgeon. Ongoing basic research studies have demonstrated a dose-dependent and time-dependent cardioprotective effect of erythropoietin (EPO) administration during surgery in the infant rabbit model (Shi et al, 2004; Rafiee et al, 2005). A rat model of ischemic-reperfusion injury further delineated the dose-dependent cardioprotective effect of EPO (Baker et al, 2007). Neuroprotective effects of EPO have been demonstrated by other research teams using various animal models (Aydin et al, 2003; Catania et al, 2002). Based on the bench research, John Baker, PhD, professor of Cardiothoracic Surgery at the Medical College of Wisconsin, and Steve Zangwill, MD, assistant professor of Pediatric Cardiology at the Medical College of Wisconsin, have designed a study to test the hypothesis that a single dose of EPO during surgery prior to crossclamp and cardiopulmonary bypass will protect the infant human heart and brain from ischemic injury.

The study's specific aim is to determine the ability of EPO to reduce injury in the heart and brain following surgical repair of congenital cyanotic and acyanotic heart defects. The study will be done in the cardiac operating room at Children's Hospital of Wisconsin in a randomized, blinded, placebo-controlled study. Reduction of injury will be determined by a decrease in biochemical indices of heart and brain injury and an improvement in systolic and diastolic heart function. Atrial tissue (surgical discards) will be analyzed to determine the molecular mechanisms underlying EPO-induced cardioprotection.

The study population will include 120 children between the ages of 6 weeks and 5 years who are hospitalized for reparative cardiac surgery requiring cardiopulmonary bypass and aortic cross-clamping. Children with cyanotic heart disease will be differentiated from those with acyanotic lesions. Each child then will be randomized to receive either study drug or placebo. This will result in two groups of children with cyanotic lesions and two with acyanotic heart disease. During surgery, EPO or placebo will be administered just prior to placing the child on cardiopulmonary bypass, and either EPO or placebo will be included in the pump prime solution. It is expected that the modified ultra-filtration will remove nearly all EPO from the bloodstream at the conclusion of cardiopulmonary bypass. Blood specimens drawn at baseline, intraoperatively and at prescribed intervals postoperatively will be analyzed for biochemical indices of heart and brain injury, including EPO levels, brain natriuretic protein, s100b, neuron-specific enolase and Troponin I. Echocardiograms will be utilized to assess systolic and
diastolic heart function.

Testing erythropoietin for its cardioprotective and neuroprotective effects in children undergoing cardiac surgery including cardiopulmonary bypass is a step toward establishing better outcomes for these children in terms of physical and cognitive development. Long-term follow-up of this cohort with developmental, cognitive and quality of life assessments may be a future research objective.

The Erythropoietin and Pediatric Cardiac Surgery study has been approved by the Human Research Review Board and has received funding through Children's Research Institute and the General Clinical Research Center. The clinical trial is registered at www.clinicaltrials.gov. The research team hopes to begin recruitment in July 2007, and it is expected to continue for about two years. 

References
Aydin, A, Genc, K, Akhisaroglu, M, Yorukoglu, K, Gokmen, N, Gonullu, E. Erythropoietin exerts, neuroprotective effect in neonatal rat model of hypoxic-ischemic injury. Brain Dev. 25: 494-498; 2003.

Baker, JE, Kozik, D, Hsu, AK, Fu, X, Tweddell, J S, Gross, GJ. Darbepoetin alfa protects the rat heart against infarction: Dose-response, phase of action, and mechanisms. Journal of Cardiovascular Pharmacology. 49(6), 337-345; 2007.

Catania, MA, Marciano, MC, Parisi, A, Sturiale, A, Buemi, M, Grasso, G, Squadrito, F, Caputi, AP, Calapai, G. Erythropoietin prevents cognition impairment induced by transient brain ischemia in gerbils. Eur J Pharmacol. 437: 147-150; 2002.

Rafiee, P, Shi, Y, Su, J, Pritchard Jr, K, Tweddell, JS, Baker, JE. Erythropoietin protects the infant heart against ischemia-reperfusion injury by triggering multiple signaling pathways. Basic Res Cardiol. 100: 187-197; 2005.

Shi, Y, Rafiee, P, Su, J, Pritchard Jr, K, Tweddell, J, Baker, J. Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels. Basic Res Cardiol. 99: 173-182; 2004.

Rapid Response Team

By Karen Fry, patient care supervisor, Pediatric Intensive Care Unit, Children's Hospital of Wisconsin

The Rapid Response Team (RRT) initiative was developed as part of the Institute for Health Care Improvement 100,000 Lives Campaign. It is comprised of a group of health care professionals with critical care expertise and experience who are prepared to respond to patients at the first sign of deterioration before respiratory and/or cardiac arrest occurs. This program was designed to elevate the level of care we provide to patients at Children's Hospital of Wisconsin.

Why?
Studies have shown that an arrest is almost always preceded by a period of instability, averaging 6.5 hours. The goal is to identify patients at risk and intervene.

Who?
The RRT is available 24 hours a day, seven days a week. If a transport team is in house, a transport registered nurse (RN) and respiratory care practitioner (RCP) will respond as RRT 1. If transport is unavailable, RRT 2 will respond, which is composed of a Pediatric Intensive Care Unit (PICU) RN and RCP. Medical control will function as the physician member of the team and will attempt to respond to all calls. The admitting resident and house supervisor also will be notified via pager to ensure complete coverage.

Criteria and situations for the RRT:

• Acute changes in respiratory status, heart rate, blood pressure, oxygenation or mental status.
• Additional evaluation of the patient is needed.
• Failure of the patient to respond to treatment.
• More than one STAT page is required to assemble the proper care team.
• Response from the primary chain of command still leaves the caregiver concerned.
• Staff is concerned about a patient.

Who activates the RRT?
At this time, nurses, residents, attending physicians and respiratory therapists from the inpatient care units, the intermediate care unit and Day Surgery can activate this service. Dialing the Transport and Physician Referral Center activates a team. The team arrives promptly and begins assessment. If a critical care physician is unable to respond, he or she will communicate via phone and will send a designee if needed.

What is the responder's role?
The responders will obtain information from the requestor regarding the situation and background and complete an assessment. They will obtain orders and perform interventions if needed and further communicate their recommendations. They will respond by educating and supporting the patient care team and facilitate communication with the patient's physician. If necessary, they will assist with transfer to a higher level of care. Transport will conduct a 12 to 24 hour follow up to assess the patient's condition.

How will we know if it's working?
Success will be measured through data collection. Our goal is to reduce the number of codes outside the PICU and Neonatal Intensive Care Unit (NICU) and reduce the number of unplanned emergent floor to PICU transfers by 25 percent. Feedback surveys will be e-mailed to responders. The goal is to achieve a requestor and responder satisfaction of 85 percent.

Both requestors and responders have received education through online education and question and answer sessions, facilitated by Karen Fry (PICU), Julie Halvorson (RT), Robyn Saxe (Transport) and Judy Gamalski (Quality Improvement). The PICU is piloting the program with approximately 40 RNs. In addition, sessions were extended to leadership and medical teams. The program launched Monday, June 18. 

Monoclonal antibodies for solid organ transplant

By Sonia Peterson, PharmD, Children's Hospital of Wisconsin

Immunosuppression is vital for graft survival after solid organ transplantation. Acute rejection episodes occur in more than 50 percent of all pediatric transplant recipients.

After transplant, the allograft releases foreign antigens that are recognized by the host's immune system and presented to T-cells. Activation of T-cells results in the expression of the high affinity interleukin-2 (IL-2) receptor. The interleukin-2 receptor consists of three transmembrane protein chains: (CD25), (CD122) and (CD132). When interleukin-2 (a cytokine) binds to the receptor, T-cells undergo clonal expansion and infiltrate the allograft resulting in acute rejection.

Basiliximab and daclizumab, IgG monoclonal antibodies to the interleukin-2 (IL-2) receptor, were approved to prevent acute rejection after renal transplantation. Both specifically block the (CD25) portion of the IL-2 receptor and prevent the clonal expansion of T-cells.

References

• Berard, JL, Velez, RL, Freeman, RB, Tsunoda, SM. A review of interleukin-2 receptor antagonists in solid organ transplantation. Pharmacotherapy. 19(10):1127-37, 1999 Oct.
• Dharnidharka, VR. Pediatric kidney transplantation literature review 2006. Pediatr Transplantation. 2007: 11: 354–365.
• Micromedex® Healthcare Series: MICROMEDEX, Greenwood Village, Colorado (Edition expires [06/2007]).
• Shapiro, R. Pediatric renal transplantation: Review of recent literature. Curr Opin Organ Transplant. 2000, 5: 324-329.
• Simulect® [package insert].  East Hanover, NJ: Novartis; 2005.
• Tejani, A, Sullivan, EK. The impact of acute rejection on chronic rejection. A report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant. 2000, 4: 107-111.
• Vella, J. Transplant immunobiology. In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley, MA, 2007.
• Vincenti, F, Kirkman, R, Light, S, Bumgardner, G, Pescovitz, M, Halloran, P, Neylan, J, Wilkinson, A, Ekberg, H, Gaston, R, Backman, L, Burdick, J. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. New England Journal of Medicine. 338(3):161-5, 1998 Jan 15.
• Zenapax® [package insert]. Nutley, NJ: Roche; 2003.

For more information, contact Sonia Peterson at speterson@chw.org or Jen Williams at jwilliams@chw.org.