Chase R. Brown

Growing Single-Center Experience With Lung Transplantation Using Donation After Cardiac Death

BACKGROUND Early experience with lung transplantation (LTx) using organs from donors after cardiac death (DCD) has been promising, although widespread adoption has been slow because of the perception of diminished organ quality. Some centers have even suggested that use of DCD lungs is high risk and have recommended ex vivo evaluation before transplantation. We analyzed our growing single-center experience with DCD lungs procured and transplanted using protocols established for brain-dead donors. METHODS From August 2004 to July 2011, 605 patients underwent LTx, 32 (4.9%) with DCD organs. Standardized donor selection, procurement, and preservation protocols established for brain-dead donors were applied to DCD organs. Measured outcomes were Kaplan-Meier survival, early graft function measured by arterial partial pressure of oxygen/fraction of inspired oxygen (PO2/FIO2 ratio [P/F ratio]), airway complications, spirometry, and development of bronchiolitis obliterans syndrome (BOS). RESULTS Survival was 97% at 30 days, 91% at 1 year, 91% at 2 years, and 71% at 3 and 4 years. Mean P/F ratio at 6 hours and 24 hours was 305 and 332, respectively. One airway complication required intervention. Median time to extubation, intensive care unit (ICU), and total hospital lengths of stay were 1, 4, and 14 days, respectively. At median follow-up of 2.8 years, median forced expiratory volume in 1 second, percent of predicted (FEV1%) of the survivors was 59% (range, 27%-113%), with 16% (5/32) having BOS. CONCLUSIONS This growing experience suggests that recipient survival and early graft function using DCD lungs is excellent and has occurred without significant adjustment of procurement, preservation, or implantation protocols. Concerns over diminished organ quality are unfounded, and use of DCD lungs should be expanded.

Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.

Extracorporeal membrane oxygenation (ECMO) is rarely used as a bridge to lung transplantation (BTT) because of its associated morbidity and mortality. However, recent advancements in perfusion technology and critical care have revived interest in this application of ECMO. We retrospectively reviewed our utilization of ECMO as BTT and evaluated our early and midterm results. Nineteen patients were placed on ECMO with the intent to transplant of which 14 (74%) were successfully transplanted. Early and midterm survival of transplanted patients was 75% (1 year) and 63% (3 years), respectively, with the most favorable results observed in interstitial lung disease patients supported in the venovenous configuration. Extracorporeal membrane oxygenation–bridged transplant survival rates were equivalent to nonbridged recipients, but early morbidity and mortality are high and the failure to bridge to transplant is significant. Overall, successfully bridged patients can derive a tangible benefit, albeit with considerable consumption of resources.

Bone marrow support of the heart in pressure overload is lost with aging.

Rationale Exogenous stem cell delivery is under investigation to prevent and treat cardiac dysfunction. It is less studied as to the extent endogenous bone marrow derived stem cells contribute to cardiac homeostais in response to stress and the affects of aging on this stress response. Objective To determine the role of bone marrow (BM) derived stem cells on cardiac homeostasis in response to pressure overload (PO) and how this response is altered by aging. Methods and Results Young (8 weeks) and old (>40 weeks) C57/b6 mice underwent homo- and heterochronic BM transplantation prior to transverse aortic constriction (TAC). We found that older BM is associated with decreased cardiac function following TAC. This decreased function is associated with decrease in BM cell engraftment, increased myocyte apoptosis, decreased myocyte hypertrophy, increased myocardial fibrosis and decreased cardiac function. Additionally, there is a decrease in activation of resident cells within the heart in response to PO in old mice. Interestingly, these effects are not due to alterations in vascular density or inflammation in response to PO or differences in ex vivo stem cell migration between young and old mice. Conclusions BM derived stem cells are activated in response to cardiac PO, and the recruitment of BM derived cells are involved in cardiac myocyte hypertrophy and maintenance of function in response to PO which is lost with aging.

Family history of aortic disease predicts disease patterns and progression and is a significant influence on management strategies for patients and their relatives.

BACKGROUND While a positive family history (FH) is a known risk factor for developing an aneurysm, its association with the extent of disease has not been established. We evaluated the influence of a FH of aortic disease with respect to the pattern and distribution of aortic aneurysms in a given patient. METHODS AND RESULTS From November 1999 to November 2011, 1263 patients were enrolled in physician-sponsored endovascular device trials to treat aortic aneurysms. Of the 555 patients who were alive and returning for follow-up, we obtained 426 (77%) family histories. Three-dimensional imaging studies were used to identify the presence of aneurysms; 36% (155/426) of patients had a FH of aortic aneurysms and 5% (21/155) had isolated intracranial aneurysms. A logistic regression model was used to compare aortic morphology between patients with a positive or negative FH for aneurysms. Patients with a positive FH of aortic aneurysms were younger at their initial aneurysm (63 vs 70 years; P < .0001), more frequently had proximal aortic involvement (root: odds ratio [OR], 5.4; P < .0001; ascending: OR, 2.9; P < .001; thoracic: OR, 2.2; P = .01) with over 50% of FH patients ultimately developing suprarenal aortic involvement (P = .0001) and had a greater incidence of bilateral iliac artery aneurysm (OR, 1.8; P = .03). CONCLUSIONS FH is an important tool that provides insight into the expected behavior of the untreated aorta and has significant implications for the development of treatment strategies. These findings should be used to guide patients management with regard to treatment, follow-up paradigms, genetic testing, and screening of other family members.

Splenic artery embolization for the treatment of refractory ascites after liver transplantation

Refractory ascites (RA) is a challenging complication after orthotopic liver transplantation. Its treatment consists of the removal of the precipitating factors. When the etiology is unknown, supportive treatment can be attempted. In severe cases, transjugular intrahepatic portosystemic shunts, portocaval shunts, and liver retransplantation have been used with marginal results. Recently, splenic artery embolization (SAE) has been described as an effective procedure for reducing portal hyperperfusion in patients undergoing partial or whole liver transplantation. Here we describe our experience with SAE for the treatment of RA. Between June 2004 and June 2010, 6 patients underwent proximal SAE for RA. Intraoperative flow measurements, graft characteristics, embolization portal vein (PV) velocities before and after SAE, and spleen/liver volume ratios were collected and analyzed. The response to treatment was assessed with imaging (ultrasound/computed tomography) and on the basis of clinical outcomes (weight changes, diuretic requirements, and the time to ascites resolution). The PV velocity decreased significantly for each patient after the embolization (median = 66.5 cm/second before SAE and median = 27.5 cm/second after SAE, P < 0.01). All patients experienced a significant postprocedural weight loss (mean = 88.1 ± 28.4 kg before SAE and mean = 75.8 ± 28.4 kg after SAE, P < 0.01) and a dramatic decrease in their diuretic requirements. All but 1 of the patients experienced a complete resolution of ascites after a median time of 49.5 days (range = 12‐295 days). No patient presented with postembolization complications. In conclusion, SAE was effective in reducing the PV velocity immediately after the procedure. Clinically, this translated into a dramatic weight loss, a reduction of diuretic use, and a resolution of ascites. SAE appears to be a safe and effective treatment for RA. Liver Transpl 17:668–673, 2011.

High incidence of upper-extremity deep vein thrombosis with dual-lumen venovenous extracorporeal membrane oxygenation

Venovenous extracorporealmembrane oxygenation (ECMO) has emerged as an important intervention for patients with acute respiratory failure, as well as as a bridge to lung transplantation for end-stage lung disease. A recently introduced bicaval, dual-lumen cannula appears to be a promising technologic advancement for venovenous ECMO support. Introduced percutaneously through the right internal jugular or left subclavian vein, the Avalon Elite cannula (Avalon Laboratories, Rancho Dominguez, Calif) selectively drains venous blood from the inferior and superior venae cavae and infuses oxygenated blood directly into the right atrium. Advantages of this cannula include a single insertion and upper body placement, which can allow ambulation to maintain patient conditioning.Although the cannula is available inmultiple sizes (23-31F), clinical experience has shown that larger cannula sizes are required to generate adequate flow for respiratory support in adults (>4.0 L/min). Larger cannulas used for extended durations, however, probably predispose the patient toward upper-extremity deep venous thrombosis (DVT). We evaluated the incidence and subsequent clinical implications of upper extremity DVT in patients who were supported with venovenous ECMO by means of the Avalon dual-lumen cannula.

Timing of Heparin and Thrombus Formation in Donor Lungs after Cardiac Death

BACKGROUND Heparin is routinely administered to brain-dead donors before cardiac arrest, although it is not universally allowed for donation after cardiac death (DCD) donors due to concerns that death may be hastened. The lack of heparin may lead to thrombosis and compromised graft function. We evaluated the impact of timing of heparin administration and thrombi formation in a DCD pig model. METHODS Eight domestic adult pigs were administered systemic heparin (30,000 IU): four prior to cardiac arrest through intravenous injection (prearrest heparin) and four after cardiac arrest via injection into the right atrium followed by open cardiac massage (postarrest heparin). Pigs were euthanized with potassium chloride and a minimum of 5 minutes of cardiac silence allowed before organ procurement. Lungs were flushed with antegrade and retrograde Perfadex, and pulmonary preservation solution effluent was evaluated for gross thrombi. Organs were fixed in formalin, sagittally sectioned, and evaluated by a pulmonary pathologist blinded to treatment. RESULTS Antegrade and retrograde flushes demonstrated no significant thrombi. Gross pathologic evaluation revealed no occlusive central thrombi. Scant peripheral thrombi were detected in both treatment groups. No microscopic thrombi were noted in either treatment group. CONCLUSIONS Delayed heparin administration after cardiac death does not affect thrombus formation in an animal model of lung procurement after cardiac death. Concern about clinically significant thrombosis occurring when heparin is not given before cardiac arrest appears unfounded. These findings suggest that DCD lungs can be used regardless of antemortem heparin administration.

Donor lungs with pulmonary embolism evaluated with ex vivo lung perfusion.

Acute pulmonary embolism (PE) compromises oxygenation and is typically considered a contraindication to lung donation for transplantation. We report the use of ex vivo lung perfusion (EVLP) to evaluate and possibly improve a pair of donor lungs with PE and poor oxygen exchange to a condition that might have been suitable for subsequent transplantation. A pair of donor lungs was procured for research after being declined for clinical use and placed on the EVLP circuit for 7 hours. Functional monitoring of the lungs revealed an increase in the partial pressure of oxygen to fraction of inspired oxygen ratio (P/F ratio) from 268 in situ to 458 after EVLP. While on the circuit, pulmonary vascular resistance decreased as dynamic compliance of the lungs increased, suggesting they might have been acceptable for transplantation.

Outcomes after single lung transplantation in older patients with secondary pulmonary arterial hypertension.

Although the International Society for Heart and Lung Transplantation (ISHLT) guidelines recommend 65 years as the upper age limit for lung transplantation (LTx), centers have transplanted allografts in older patients, with outcomes comparable to those of younger patients. Coexisting pulmonary arterial hypertension (PAH) complicates decisions to proceed with single LTx (SLTx) in older patients and might preclude transplantation altogether in some patients. To address this, patients agedZ 65 years who underwent SLTx at our institution were studied to understand the effect of secondary PAH on outcome.

Pediatric donor lungs for adult transplant recipients: feasibility and outcomes.

BACKGROUND There is a limited experience using pediatric organs for adult lung transplantation (LTx), with size matching the major concern. We reviewed our experience transplanting pediatric donor lungs into adult recipients with endpoints of post-LTx complications and overall patient survival. METHODS From 2/1990 to 12/2007, 609 adults underwent primary LTx at our institution. Thirty-eight (6.2%) patients underwent LTx with organs from pediatric donors (≤16 years). Of these, median donor age was 13 years (range: 7 to 16) and median recipient age 55 (range: 24 to 66). Endpoints analyzed included size matching accuracy, airway and pleural complications, time to extubation, intensive care unit (ICU) and hospital lengths of stay, as well as survival. RESULTS Gross undersizing of the donor lung was present in 2/38 (5.3%) and of the donor bronchus in 11/38 (29%). Five patients (13%) experienced a major postoperative airway complication. Thoracentesis prior to discharge was necessary in 4/38 (11%) patients and chest tube reinsertion in 10/38 (26%) for pleural effusion. Median time to extubation was 2 days. ICU and hospital lengths of stay were 6 and 16 days, respectively. Kaplan-Meier survival at 30 days, 1 year, 3 years, and 5 years post-transplant was 89%, 74%, 63%, and 55%. CONCLUSIONS Despite sizing concerns, transplantation of pediatric lungs into adult recipients is feasible. Size mismatch may predispose to higher rates of airway and pleural complications. Hospital course and overall survival appear comparable to adult-to-adult LTx, and concerns over size matching should not preclude pediatric organ use for adult candidates.