The OPTN Deceased Donor Potential Study: Implications for Policy and Practice.

The Organ Procurement and Transplantation Network (OPTN) Deceased Donor Potential Study, funded by the Health Resources and Services Administration, characterized the current pool of potential deceased donors and estimated changes through 2020. The goal was to inform policy development and suggest practice changes designed to increase the number of donors and organ transplants. Donor estimates used filtering methodologies applied to datasets from the OPTN, the National Center for Health Statistics, and the Agency for Healthcare Research and Quality and used these estimates with the number of actual donors to estimate the potential donor pool through 2020. Projected growth of the donor pool was 0.5% per year through 2020. Potential donor estimates suggested unrealized donor potential across all demographic groups, with the most significant unrealized potential (70%) in the 50-75-year-old age group and potential Donation after Circulatory Death (DCD) donors. Actual transplants that may be realized from potential donors in these categories are constrained by confounding medical comorbidities not identified in administrative databases and by limiting utilization practices for organs from DCD donors. Policy, regulatory, and practice changes encouraging organ procurement and transplantation of a broader population of potential donors may be required to increase transplant numbers in the United States.

Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management.

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

Diagnosis and management of tuberculosis in transplant donors: a donor-derived infections consensus conference report.

Mycobacterium tuberculosis is a ubiquitous organism that infects one-third of the world's population. In previous decades, access to organ transplantation was restricted to academic medical centers in more developed, low tuberculosis (TB) incidence countries. Globalization, changing immigration patterns, and the expansion of sophisticated medical procedures to medium and high TB incidence countries have made tuberculosis an increasingly important posttransplant infectious disease. Tuberculosis is now one of the most common bacterial causes of solid-organ transplant donor-derived infection reported in transplant recipients in the United States. Recognition of latent or undiagnosed active TB in the potential organ donor is critical to prevent emergence of disease in the recipient posttransplant. Donor-derived tuberculosis after transplantation is associated with significant morbidity and mortality, which can best be prevented through careful screening and targeted treatment. To address this growing challenge and provide recommendations, an expert international working group was assembled including specialists in transplant infectious diseases, transplant surgery, organ procurement and TB epidemiology, diagnostics and management. This working group reviewed the currently available data to formulate consensus recommendations for screening and management of TB in organ donors.

Current practices and evaluation of screening solid organ donors for West Nile virus.

The first cases of West Nile virus (WNV) transmitted through solid organ transplantation (SOT) were identified in 2002. Subsequently, 5 additional clusters have been reported to public health officials in the United States. Based upon a limited number of known cases, patients who acquire WNV from infected donor organs might be at higher risk for severe neurologic disease and death, compared with patients infected through mosquito bites. In response, some organ procurement organizations (OPOs) have instituted pre-transplant screening of organ donors for WNV infection. We evaluated the current practices, concerns, and challenges related to screening organ donors for WNV in the United States by reviewing the relevant medical literature and interviewing key stakeholders. Screening organ donors for WNV is not required by national policy. In 2008, 11 (19%) of 58 OPOs performed WNV screening using nucleic acid amplification testing (NAT). These OPOs differ in their screening strategies, NAT performed, and logistical challenges. Concerns of delays in receiving NAT results before transplant and potential false-positive results leading to organ wasting are limitations to more widespread screening. Furthermore, it is unknown if WNV screening practices decrease SOT-related morbidity and mortality, or if screening is cost-effective. Additional data are needed to assess and improve transplant outcomes related to WNV.

Development of donor yield models.

Increasing donor yield, or the number of organs transplanted per donor, has been a focus of the transplant community in recent years. However, an exclusive focus on observed yield, unadjusted for the donor characteristics, ignores important differences between donors and donor case mixes in donation service areas (DSAs). We analyzed deceased donor registry data from the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients from January 2006 to December 2009 (N = 32 116 donors). Overall yields and kidney yields were modeled using ordinal logistic regression, and logistic regression was used to model heart, lung, pancreas and liver yields. Donor characteristics, including demographics, historical information and positive serology were related to overall and organ-specific yield. This study shows the potential value of the yield models as evaluation metrics and as tools that can inform DSA-wide practices in donor management and can improve organ utilization.

Nucleic acid testing (NAT) of organ donors: is the 'best' test the right test? A consensus conference report.

Nucleic acid testing (NAT) for HIV, HBV and HCV shortens the time between infection and detection by available testing. A group of experts was selected to develop recommendations for the use of NAT in the HIV/HBV/HCV screening of potential organ donors. The rapid turnaround times needed for donor testing and the risk of death while awaiting transplantation make organ donor screening different from screening blood-or tissue donors. In donors with no identified risk factors, there is insufficient evidence to recommend routine NAT, as the benefits of NAT may not outweigh the disadvantages of NAT especially when false-positive results can lead to loss of donor organs. For donors with identified behavioral risk factors, NAT should be considered to reduce the risk of transmission and increase organ utilization. Informed consent balancing the risks of donor-derived infection against the risk of remaining on the waiting list should be obtained at the time of candidate listing and again at the time of organ offer. In conclusion, there is insufficient evidence to recommend universal prospective screening of organ donors for HIV, HCV and HBV using current NAT platforms. Further study of viral screening modalities may reduce disease transmission risk without excessive donor loss.

Organ donation and utilization in the United States: 1998-2007.

Organ transplantation remains the only life-saving therapy for many patients with organ failure. Despite the work of the Organ Donation and Transplant Collaboratives, and the marked increases in deceased donors early in the effort, deceased donors only rose by 67 from 2006 and the number of living donors declined during the same time period. There continue to be increases in the use of organs from donors after cardiac death (DCD) and expanded criteria donors (ECD). This year has seen a major change in the way organs are offered with increased patient safety measures in those organ offers made by OPOs using DonorNet. Unfortunately, the goals of 75% conversion rates, 3.75 organs transplanted per donor, 10% of all donors from DCD sources and 20% growth of transplant center volume have yet to be reached across all donation service areas (DSAs) and transplant centers; however, there are DSAs that have not only met, but exceeded, these goals. Changes in organ preservation techniques took place this year, partly due to expanding organ acceptance criteria and increasing numbers of ECDs and DCDs. Finally, the national transplant environment has changed in response to increased regulatory oversight and new requirements for donation and transplant provider organizations.

Far-field auditory evoked potentials in near-miss sudden infant death syndrome.

Auditory evoked potentials (AEPs) were determined in 16 patients with near-miss sudden infant death syndrome. The AEPs were normal in all patients except one with prolonged 1 to V interpeak latency (bilaterally) and another with an asymmetry of interear 1 to V interpeak latency difference. These results indicate that AEPs do not permit detection of infants at high risk for crib death.

Cerebrospinal fluid endorphins and the infant apnea syndrome.

Cerebrospinal fluid (CSF) beta-endorphin levels were determined in 16 patients with infant apnea syndrome and 34 control patients. A statistically significant difference (P less than or equal to .0001) was found with the infant apnea syndrome patients having beta-endorphin levels of 14.7 +/- 1.2 pmol/L (mean +/- SE) and the controls having levels of 6.9 +/- 0.6 pmol/L (mean +/- SE). To test whether these elevated CSF beta-endorphin levels were the result or the possible cause of the apneas, three patients with infant apnea syndrome and abnormal CSF beta-endorphin levels participated in a study to determine whether a continuous low-dose infusion (10 micrograms/kg/h) of the narcotic antagonist naloxone would reduce the occurrence of apneas and respiratory pauses during all-night polysomnogram recordings. A fourth patient with documented apneas but normal CSF beta-endorphin levels was also studied while on a regimen of naloxone. In the patients with infant apnea syndrome and abnormal CSF beta-endorphin levels, a significant (P less than or equal to .05) reduction in apneas and respiratory pauses occurred during naloxone infusion. There was no change in the occurrence of apneas or respiratory pauses during naloxone infusion in the patient with normal CSF endorphin levels. Abnormal CSF levels of endorphins may play a role in apneas of infancy and may be amenable to therapy with narcotic antagonists.

Osteoid osteoma in children and young adults.

Osteoid osteoma is a relatively common benign tumor of bone which occurs most often in adolescents and young adults. The pattern of the pain with its characteristic response to aspirin and the roentgenographic findings make the clinical diagnosis easy and virtually certain. An example is presented to help the pediatrician become familiar with the tumor and its diagnosis.

Urine mercury levels in Kawasaki disease.

Six patients with diagnostic criteria for Kawasaki disease had abnormally high urinary excretions of mercury. They were compared by age, sex, and geographic location with matched controls. Improvement of one patient was temporally related to chelation of mercury with penicillamine. There are numerous clinical similarities between acrodynia and Kawasaki disease and the appearance of the mucocutaneous lymph node syndrome (Kawasaki disease) has been related temporally and geographically to environmental pollution with mercury. The mucocutaneous lymph node syndrome (Kawasaki disease) may represent a disease caused by environmental pollution with mercury, or clinical symptoms compatible with Kawasaki disease may indicate environmental exposure to mercury.

A catch in the Reye.

Twenty-six cases of Reye syndrome from The Children's Hospital, Camperdown, Australia, occurring between 1973 and 1982 were reviewed. Of these, 20 cases met the US Public Health Service Centers for Disease Control criteria for the diagnosis of Reye syndrome. Aspirin or salicylate ingestion had occurred in only one of the 20 cases (5%), and paracetamol (acetaminophen) had been administered in only six of the cases (30%). Pathologic confirmation of the diagnosis of Reye syndrome was accomplished in 90% of the cases. The incidence of Reye syndrome in New South Wales, Australia, is estimated from this study to be approximately nine cases per 1 million children compared with recent US data of ten to 20 cases per 1 million children and three to seven cases per 1 million children in Great Britain. The mortality for these Reye syndrome cases in Australia was 45% as compared with a 32% case-fatality rate in the United States. In Australia, the pediatric usage of aspirin has been extremely low for the past 25 years (less than 1% of total dosage units sold), with paracetamol (acetaminophen) dominating the pediatric analgesic and antipyretic market. Reye syndrome may be disappearing from Australia despite a total lack of association with salicylates or aspirin ingestion, since there were no cases found at The Children's Hospital in 1983, 1984, or 1985.

Wegener's granulomatosis in the pediatric age group.

Six cases of Wegener's granulomatosis (WG) occurring in patients younger than 21 years are described. Only 11 other cases in the pediatric age group have been reported, and all 17 of these patients had the onset of the disease during the second decade of life. Wegener's granulomatosis is a systemic disease characterized by a clinical triad of paranasal sinus and nasal mucosa involvement, pulmonary infiltration and cavitation, and renal disease with hematuria. The most common presenting symptoms are malaise and fever, sinusitis, epistaxis, and hematuria. Most patients have roentgenographic evidence of pulmonary and sinus disease and laboratory evidence of renal involvement on initial evaluation. The prognosis of WG was formerly dismal; more than 90% of patients died in less than two years, but with recent therapeutic regimens, more than 50% of these patients are surviving. The treatment we recommend consists of nitrogen mustard with adrenocorticotropic hormone or prednisone for the induction of remission, followed by cyclophosphamide and prednisone as maintenance drugs. This regimen has proved effective in inducing a remission in four of four patients.

The effects of pharmaceutical firm enticements on physician prescribing patterns. There's no such thing as a free lunch.

We examined the impact on physician prescribing patterns of pharmaceutical firms offering all-expenses-paid trips to popular sunbelt vacation sites to attend symposia sponsored by a pharmaceutical company. The impact was assessed by tracking the pharmacy inventory usage reports for two drugs before and after the symposia. Both drugs were available only as intravenous preparations and could be used only on hospitalized patients. The usage patterns were tracked for 22 months preceding each symposium and for 17 months after each symposium. Ten physicians invited to each symposium were interviewed about the likelihood that such an enticement would affect their prescribing patterns. A significant increase in the prescribing pattern of both drugs occurred following the symposia. The usage of drug A increased from a mean of 81 +/- 44 units before the symposium to a mean of 272 +/- 117 after the symposium (p less than 0.001). The usage of drug B changed from 34 +/- 30 units before the symposium to 87 +/- 24 units (p less than 0.001) after the symposium. These changed prescribing patterns were also significantly different from the national usage patterns of the two drugs by hospitals with more than 500 beds and major medical centers over the same period of time. These alterations in prescribing patterns occurred even though the majority of physicians who attended the symposia believed that such enticements would not alter their prescribing patterns.

The pathophysiologic changes following bile aspiration in a porcine lung model.

Aspiration of bile is an underpublicized aspiration syndrome. Using a porcine lung model, the physiologic response and the histopathology of lung tissue were evaluated after the intratracheal instillation of sublethal doses of bile. Twenty-one domestic swine (11 to 19 kg) were the studied population. Three groups of five swine were evaluated: a control group received intratracheal physiologic saline (pH 7.45); study group 1 received strained gastric contents (pH 2.24); and study group 2 received strained bile (pH 7.19). All animals received the solutions at 0.5 ml/kg intratracheally. Lungs of six additional animals were studied (two gastric, two bile, and two physiologic saline) after aspiration by scanning electron microscopy (SEM). A seventh untreated animal was used as the SEM control. The physiologic data were analyzed using analysis of variance for repeated measures. The SEM and histopathologic results were graded by an observer blinded to the groups and were analyzed using the analysis of variance (ANOVA) and Scheffe tests. The group with bile aspiration was consistently characterized by significant deterioration of PaO2, the alveolar-arterial (A-a) gradient, shunt fraction, and static compliance (p < 0.01); and the light histopathologic and SEM findings demonstrated pathologic changes in the bile-exposed lung (p < 0.05) greater than the gastric- or saline-exposed lungs. It is concluded that bile aspiration produces a severe chemical pneumonitis leading to noncardiac pulmonary edema.

Endobronchial and parenchymal juvenile laryngotracheobronchial papillomatosis. Effect of photodynamic therapy.

Juvenile laryngotracheobronchial papillomatosis (JLTBP) is a recurrent, prolonged disease usually confined to the upper airway. Rarely, tracheobronchial tree or lung parenchymal involvement occurs. The various therapeutic interventions are often unsuccessful once extralaryngeal involvement becomes apparent. Photodynamic therapy (PDT) has been successful in eradicating JLTBP in a few case reports. We present a case of extensive JLTBP with parenchymal involvement treated with multiple courses of PDT. We demonstrated temporary regression of endobronchial papillomas, but no change in parenchymal lesions. Recurrent endobronchial disease was most likely related to reinfection from parenchymal lesions inaccessible to PDT.

Effect of measurement error on calculated variables of oxygen transport.

The effect of measurement error in pH, PCO2, and PO2 on mathematically derived variables of oxygen transport in patients was delineated by comparing calculated oxygen saturations from a blood-gas machine with measured saturations from a CO-oximeter and further by modeling the error in a computer simulation. Twenty-one critically ill patients aged 30-84 yr were studied. A total of 80 arterial and 80 mixed venous blood gas samples were collected. The intraclass correlation results between measured and calculated arterial (SaO2) and mixed venous (Sv-O2) oxygen saturations were 0.59 and 0.68, respectively. The product-moment correlation for SaO2 was 0.75 and for Sv-O2 was 0.77. The percent error in calculating and measuring oxygen saturation was found to be greater at low PO2 values, whereas percent error of calculating oxygen consumption increased as the PO2 increased. Measurement repeatability at high PO2 is better than at low PO2 for both measured and calculated methods. We conclude from this comparison that measured and calculated SaO2 and Sv-O2 values are not interchangeable. Each can introduce substantial error in calculating oxygen consumption through error propagation and error amplification.

Practical reduction of transplantation costs. Use of commercial transportation instead of charter aircraft for sharing pancreas grafts.

OBJECTIVE: To demonstrate cost savings in pancreas transplantation through use of commercial organ transportation. DESIGN: Retrospective study. SETTING: Independent Organ Procurement Organization, Denver, Colo. SUBJECTS: Forty-three consecutive pancreas grafts recovered by Colorado transplantation surgeons and transported via charter aircraft (53.4%) or commercial airlines (46.6%) to transplantation centers outside Colorado. MEASUREMENTS: Actuarial graft survival at 1 year was calculated. Transportation costs were also obtained. MAIN RESULTS: Transportation of organs via charter aircraft cost an average of $3658.37 compared with an average of $102.40 for commercial airline transportation (average cost difference, $3555.97). Graft survival was 73.9% for chartered grafts vs 80.0% for commercially shipped grafts. Mean preservation times were 13 hours 54 minutes for chartered grafts vs 17 hours 50 minutes for commercial transportation. CONCLUSION: Our data demonstrated a significant cost savings when pancreas grafts were transported via commercial airlines instead of chartered aircraft. These cost savings were obtained without negative sequelae in clinical outcome, encouraging widespread use of commercial airlines for transporting shared pancreas grafts.

A double-crossover study comparing conventional ventilation with high frequency ventilation in a patient with tracheoesophageal fistula.

Respiratory distress, from severe gastric aspiration pneumonitis and abdominal distention in the patient with tracheoesophageal fistula frequently requires mechanical ventilatory support. Bulk flow ventilation can lead to enlargement of the fistulous tract, elevation of gastric intraluminal pressures, raised airway pressures with hemodynamic instability, and retained secretions. We report a case of tracheoesophageal fistula, secondary to perforation of a squamous cell carcinoma of the esophagus, with temporary improvement in gas exchange on high frequency ventilation after failing on a conventional ventilator. The patient initially failed to improve on an Engstrom ventilator (Engstrom-Gambro, Inc., Barrington, IL) at 13 l/minute ventilation. Instituting high frequency jet ventilation with a VS 600 Jet Ventilator (Instrument Development Corporation, Pittsburgh, PA) at initial settings of 35 psi, rate 150, inspiratory time 40%, FiO2 0.8 and 12 cm H2O positive end expiratory pressure (PEEP), provided incremental improvement in gas exchange and oxygenation up to 26 cm H2O PEEP. However, in view of progressive multi-organ failure we terminated the jet ventilation after 48 h and returned the patient to conventional ventilation. We were unable to provide life-sustaining ventilation and oxygenation with either an Engstrom ventilator at 13 l/-minute ventilation or an MA-1 ventilator (Puritan-Bennett, Kansas City, MO) at a tidal volume of 800 cc and a ventilator rate of 30. Terminal respiratory failure occurred. Based on the period of improvement using high frequency jet ventilation, we believe this mode of ventilatory support is beneficial in the management of tracheoesophageal fistula.

Endotracheal epinephrine is unreliable.

When intravenous access cannot be obtained in an emergency, the endotracheal route of emergency drug administration can be used for epinephrine, atropine, and lidocaine. Optimal drug dosages for endotracheal administration as well as the amount and type of diluent are presently unknown. We compared central intravenous, peripheral intravenous, intraosseous, and intratracheal administration of epinephrine 1:10,000 in both normotensive and hemorrhagic shock dogs. The shock model consisted of 50% blood volume depletion over 15 min. Epinephrine was administered in a dose of 0.01 mg/kg (0.1 cc/kg) by the intraosseous route, central, and peripheral intravenous routes followed by a 5 cc normal saline flush. Intratracheal administration consisted of epinephrine 0.01 and 0.02 mg/kg diluted 1:1 and 1:2 with normal saline or sterile water and administered deep into the tracheo-bronchial tree using a 30-cm catheter. The effect of epinephrine was assessed by the response of the arterial blood pressure. Epinephrine was equally effective by the intraosseous, central intravenous, and peripheral intravenous routes in terms of time to onset of action, time to peak effect, and magnitude of effect on systolic, diastolic, and mean arterial pressures in both the shock and non-shock animals. The duration of effect was significantly longer (P less than 0.02) for the intraosseous route of administration. The endotracheal route of administration was unreliable and not reproducible in either the normotensive or shock animals. In 8/12 episodes in normotensive animals, including 5 trials with double doses of 0.02 mg/kg and dilutions of 1:1 and 1:2, and in 4/9 studies with shock animals including three with double doses, there was no discernable response of systolic or diastolic blood pressure.