Ervigio Corral

Victims of Cardiac Arrest Occurring Outside the Hospital: A Source of Transplantable Kidneys

Context Waiting lists for kidney transplants are long. Contribution This study from Madrid, Spain, compared transplantation outcomes of 584 recipients of kidneys from heart-beating donors and 320 recipients of kidneys from nonheart-beating donors who died of cardiac arrest that occurred outside the hospital. One-year (about 90%) and 5-year (about 85%) graft survival rates were similar for transplantations from nonheart-beating donors and those from heart-beating donors who were younger than 60 years of age. Cautions This retrospective study is from a center with a well-developed nonheart-beating donor transplantation program. Implications People who die of cardiac arrest that occurs outside the hospital can be a viable source for kidney transplantations. The Editors The waiting list and waiting time for transplantations will inevitably become longer as the demand for kidneys continues to exceed the supply. The kidney waiting list of the United Network for Organ Sharing currently increases at a rate of 20% per year, and the list will be 100000 to 150000 patients long by the year 2010 (1). The overall annual mortality rate for wait-listed patients for kidney transplants is estimated to be 6.3% (2). While obtaining more organs from brain-dead donors with heartbeats is necessary, additional sources of organs are also needed, which has prompted the use of the nonheart-beating donor. Nonheart-beating donors are categorized into 5 types (Appendix Table) (3). Type I and type II are considered uncontrolled donors because cardiac arrest events in these patients occur outside the hospital and, thus, the transplant team is unaware of them. In type III and type IV nonheart-beating donors, cardiac arrest is managed, or controlled, in the hospital, and the transplant team can prepare for the procurement process. In type V nonheart-beating donors, this aspect can vary. Several reports have discussed the use of nonheart-beating donors (424), and the incidence of this type of donation is increasing. However, most patients described in these studies have in-hospital cardiac arrest, and few references have been made to donors whose deaths occur outside the hospital. Appendix Table. Description of the NonHeart-Beating Donor Types (Maastricht System) In 1989, our institution (Hospital Clnico San Carlos, Madrid, Spain) began a nonheart-beating donor procurement and transplant program. Our hospital is currently the largest procurement center for this type of transplantation in Spain, supplying 46% of the nonheart-beating donor kidneys transplanted in Spain in 1997 (3, 25). Most of our donors are adults who die suddenly outside the hospital and are transferred to the hospital for the sole purpose of donation (Maastricht type I donors) (26). We aimed to compare the graft survival of kidneys from uncontrolled nonheart-beating donors (Maastricht donors type I and II) and kidneys from heart-beating donors. Methods Donor Program In 1989, our hospital started a program to obtain organs from nonheart-beating donors (3). In 1996, we signed a formal agreement with the Madrid emergency facilities (SAMUR, 061, SERCAM) and established a standard protocol for obtaining organs from persons who die suddenly outside the hospital of irreversible cardiac arrest (type I Maastricht donor category) and are transported to our center for organ donation. Before 1996, most of these persons were directly transported to the morgue, but after 1996, patients were transferred to our hospital after unsuccessful cardiovascular pulmonary resuscitation (CPR). This protocol does not affect any CPR maneuver. All measures and times specified in the established CPR procedures are undertaken, and we evaluate the patient as a potential donor only when the cardiac arrest is considered irreversible (when an effective heartbeat cannot be recovered after a stipulated period [usually 30 minutes] or when the lesions provoking the cardiac arrest are incompatible with life). The following conditions should also be met when considering a potential donor: known cause of death, ruling out violence; known time of cardiac arrest; no bleeding injuries to the thorax or abdomen to avoid blood leaks in subsequent cardiopulmonary bypass during procurement; external cardiac massage and mechanical ventilation performed within 15 minutes of the cardiac arrest; no external signs of possible intravenous drug abuse suggesting a risk for HIV, hepatitis C, or hepatitis B infection; and donor age less than 60 years. When an individual has been classified as a potential donor, the emergency team continues with cardiac massage, mechanical ventilation, and intravenous fluid perfusion to maintain adequate hemodynamic conditions during transport to our hospital. Upon arrival, the transplant coordination team checks for the conventional prerequisites for donation (for example, no infections; negative results on serologic tests for HIV and hepatitis B and C; and no tumors) and then transfers the cadaver to the operating room. In type I and type II nonheart-beating donors, the femoral vein and artery are cannulated via an incision in the right side of the groin and are connected to a cardiopulmonary bypass machine with external oxygenation and hypothermia. The maximum time of warm ischemia (from the start of cardiac arrest until bypass) should not exceed 120 minutes. Maximum pump cold perfusion time is 240 minutes. While the organ is being perfused, the transplant coordination team fulfills the legal requirements for donation. The first step is to locate the family of the deceased person and obtain consent for organ extraction. Organ retrieval is performed according to the Maastricht protocol, which requires a diagnosis of death by physicians independent of those of the procurement team and a procurement protocol approved by the local medical ethics committee according to the current organ procurement legislation. Since 1999, Spain has had a law (Real Decreto 2070/1999) that allows organ donation after cardiac arrest. Under this law, the donor can undergo cardiopulmonary bypass until the necessary consent is obtained for organ extraction. In the past year, only 7% of families declined consent for organ extraction. Study Design and Sample From January 1989 to December 2004, our center transplanted 342 kidneys from nonheart-beating donors. According to the modified Maastricht donor classification scheme (3), these graft donors are classified as follows: 273 (79.8%) type I donors (dead on arrival), 47 (13.7%) type II donors (unsuccessful resuscitation in the emergency department), 6 (1.8%) type III donors (cardiac arrest in intensive care), 4 (1.2%) type IV donors (cardiac arrest during or after a diagnosis of brain death), and 12 (3.5%) type V donors (unexpected cardiac arrest in intensive care). In our retrospective study of procedures at our center, we compared data from 320 recipients of kidneys from uncontrolled, nonheart-beating donors (type I or type II Maastricht donor category) with those from 584 recipients of kidneys from adult cadaveric heart-beating donors between January 1989 and December 2004. We divided the heart-beating donor transplants into 2 groups according to donor age: younger than 60 years of age (n= 458) and 60 years of age or older (n= 126). Figure 1 shows data on the transplantations performed per year. We excluded transplantations from types III, IV, and V nonheart-beating donors and those from heart-beating donors other than adult cadaveric donors (en bloc pediatric renal transplantations or double renal transplantations from older donors). Figure 1. Kidney transplantations at the Hospital Clnico San Carlos, Madrid, Spain, January 1989December 2004. Other transplantations are those involving other than single adult cadaveric heart-beating donors (en bloc pediatric renal transplantations or double renal transplantations from donors 60 years of age) and those involving types III, IV, and V nonheart-beating donors. Treatment and Outcome Measures We treated transplant recipients with quadruple sequential therapy (antithymocyte globulin for 7 days, azathioprine, prednisone from the time of transplantation, and cyclosporine from day 5) from January 1989 to July 1996. From July 1996 to March 2001, the immunosuppression regimen used was triple therapy with cyclosporine or tacrolimus (plus prednisone and mycophenolate). After March 2001, recipients of kidneys from nonheart-beating donors and from heart-beating donors 60 years of age or older received daclizumab and a half-dosage of tacrolimus (0.1 mg/kg of body weight per day to achieve trough levels between 5 ng/mL and 8 ng/mL) during the first 2 weeks to avoid delayed graft function, whereas recipients of kidneys from heart-beating donors younger than 60 years of age did not receive daclizumab and were treated with full-dosage tacrolimus (0.2 mg/kg per day to achieve trough levels between 8 ng/mL and 12 ng/mL). The dosages of mycophenolate and steroids were similar for the 3 groups. Hyperimmunized patients (preformed reactive antibodies 50%) were treated with the monoclonal antibody muromonab-CD3 or antithymocyte globulin. We defined delayed graft function as the need for dialysis during the immediate post-transplantation period. Patients who showed delayed graft function underwent a biopsy every 7 days until renal function started to improve. We graded acute rejection according to the Banff 97 classification (27). We treated grade I rejection (interstitial infiltration and tubulitis) with high doses of pulse steroids. We treated grade II (intimal arteritis) or grade III (transmural arteritis) rejection with either muromonab-CD3 or antithymocyte globulin. Our policy is to discharge patients when graft function starts to improve. Subsequent ambulatory patient management does not vary according to donor type. The end point of the study was graft loss, defined as nephrectomy, retransplantation, or permanent return to dialysis. We followed pa

Study design for the “effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion” (METOCARD-CNIC): A randomized, controlled parallel-group, observer-blinded clinical trial of early pre-reperfusion metoprolol administration in ST-segment elevation myocardial infarction

BACKGROUND Infarct size predicts post-infarction mortality. Oral β-blockade within 24 hours of a ST-segment elevation acute myocardial infarction (STEMI) is a class-IA indication, however early intravenous (IV) β-blockers initiation is not encouraged. In recent magnetic resonance imaging (MRI)-based experimental studies, the β(1)-blocker metoprolol has been shown to reduce infarct size only when administered before coronary reperfusion. To date, there is not a single trial comparing the pre- vs. post-reperfusion β-blocker initiation in STEMI. OBJECTIVE The METOCARD-CNIC trial is testing whether the early initiation of IV metoprolol before primary percutaneous coronary intervention (pPCI) could reduce infarct size and improve outcomes when compared to oral post-pPCI metoprolol initiation. DESIGN The METOCARD-CNIC trial is a randomized parallel-group single-blind (to outcome evaluators) clinical effectiveness trial conducted in 5 Counties across Spain that will enroll 220 participants. Eligible are 18- to 80-year-old patients with anterior STEMI revascularized by pPCI ≤6 hours from symptom onset. Exclusion criteria are Killip-class ≥III, atrioventricular block or active treatment with β-blockers/bronchodilators. Primary end point is infarct size evaluated by MRI 5 to 7 days post-STEMI. Prespecified major secondary end points are salvage-index, left ventricular ejection fraction recovery (day 5-7 to 6 months), the composite of (death/malignant ventricular arrhythmias/reinfarction/admission due to heart failure), and myocardial perfusion. CONCLUSIONS The METOCARD-CNIC trial is testing the hypothesis that the early initiation of IV metoprolol pre-reperfusion reduces infarct size in comparison to initiation of oral metoprolol post-reperfusion. Given the implications of infarct size reduction in STEMI, if positive, this trial might evidence that a refined use of an approved inexpensive drug can improve outcomes of patients with STEMI.

Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial.

STUDY OBJECTIVE We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)-administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. METHODS This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. RESULTS From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference -11.4; 95% confidence interval [CI] -18.6 to -4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference -11.1; 95% CI -21.5 to -0.6). CONCLUSION Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours.

Uncontrolled donation after circulatory death: European practices and recommendations for the development and optimization of an effective programme

The shortage of organs remains one of the biggest challenges in transplantation. To address this, we are increasingly turning to donation after circulatory death (DCD) donors and now in some countries to uncontrolled DCD donors. We consolidate the knowledge on uncontrolled DCD in Europe and provide recommendations and guidance for the development and optimization of effective uncontrolled DCD programmes.