Chetan Pasrija

Ex vivo lung evaluation of prearrest heparinization in donation after cardiac death.

Objective: To evaluate the effects of prearrest heparin administration on lung quality in a model of donation after cardiac death (DCD), and to assess the potential application of ex vivo lung perfusion (EVLP) in the identification of better grafts from the DCD donor pool. Methods: Cardiac death was induced by electric shock in 10 pigs. One group received a prearrest heparin dose of 300 units/kg (H group, n = 5) and the other did not (NH group, n = 5). Animals remained at room temperature for 1 hour without ventilation, defining the warm ischemic time. After harvest, the lungs underwent 6 hours of cold ischemia before being evaluated with EVLP for 4 hours. Results: Static compliance 28 ± 3 versus 29 ± 2 (Cstat—cm H2O), pulmonary vascular resistance (PVR) 593 ± 127 versus 495 ± 70 (PVR—dyn·s/cm5), and oxygenation 327 ± 32 versus 330 ± 28 (&Dgr;PO2—mm Hg) remained stable from the beginning until the end of EVLP in the H group. In the NH group, Cstat started to decline after the first hour (25 ± 2 vs 21 ± 2), &Dgr;PO2 after hour 2 (265 ± 44 vs 207 ± 44), and PVR started to increase after hour 3 (765 ± 132 vs 916 ± 168). Significant differences between the groups were observed at the end of EVLP (P < 0.001). Parameters of lung quality after EVLP also showed significant differences between the groups: wet weight-to-dry weight ratio (P < 0.001), protein in the bronchial lavage (P < 0.01), Na+ + K+-ATPase activity (P < 0.001), and E-selectin (P < 0.001) in the perfusate. Conclusions: Prearrest heparin administration improved organ function by preserving endothelial homeostasis. EVLP proved to be a useful platform for assessing DCD lungs, providing reliable means of discriminating injured grafts.

Repeat Sternotomy: No Longer a Risk Factor in Mitral Valve Surgical Procedures

BACKGROUND The incidence of reoperative mitral valve (MV) surgical procedures is increasing, representing more than 10% of all MV operations in the United States. Previous clinical series have reported mortality rates of 5% to 18% and reentry injury rates of 5% to 10% for reoperative MV operations. METHODS Between January 2004 and June 2012, 1,312 MV operations were performed on 1,275 patients. We excluded 234 patients who underwent small incision primary right thoracotomy, 11 redo operations with first or second operation other than sternotomy, and 10 emergent operations, leaving 1,056 MV operations for analysis (first-time sternotomy, 926 [88%]; repeat sternotomy, 130 (12%]). Preoperative computed tomography was performed for all repeat sternotomy patients. Patients at risk for reentry injury were identified, and protective strategies were applied systemically before resternotomy procedures. RESULTS Among 130 patients undergoing reoperative MV operations, 35% (46/130) had prior coronary artery bypass grafting (CABG), 15% (19/130) aortic valve operations, and 61% (80/130) MV operations. Sixteen percent (21/130) had more than one previous sternotomy. Operative mortality was 4.6% (43/926) for first-time procedures and 4.6% (6/130) for reoperative MV operations. Intraoperative injury (innominate vein) occurred during repeat sternotomy in 2 (1.5%) patients. Stroke occurred in 3 patients (2%) who underwent repeat sternotomy and in 22 (2%) who underwent first-time sternotomy. On multivariable analysis, preoperative New York Heart Association function class, concomitant CABG, dialysis, and higher pulmonary artery pressures were associated with operative mortality, and repeat sternotomy was not. CONCLUSIONS With careful planning and execution, outcomes for reoperative MV operations in contemporary practice are favorable and are identical with those for first-time operations.

Outcomes after surgical pulmonary embolectomy for acute submassive and massive pulmonary embolism: A single-center experience

Objectives: Ideal treatment strategies for submassive and massive pulmonary embolism remain unclear. Recent reports of surgical pulmonary embolectomy have demonstrated improved outcomes, but surgical technique and postoperative outcomes continue to be refined. The aim of this study is to describe in‐hospital survival and right ventricular function after surgical pulmonary embolectomy for submassive and massive pulmonary embolism with excessive predicted mortality (≥5%). Methods: All patients undergoing surgical pulmonary embolectomy (2011‐2015) were retrospectively reviewed. Patients with pulmonary embolism were stratified as submassive, massive without arrest, and massive with arrest. Submassive was defined as normotensive with right ventricular dysfunction. Massive was defined as prolonged hypotension due to the pulmonary embolism. Preoperative demographics, intraoperative variables, and postoperative outcomes were compared. Results: A total of 55 patients were identified: 28 as submassive, 18 as massive without arrest, and 9 as massive with arrest. All patients had a right ventricle/left ventricle ratio greater than 1.0. Right ventricular dysfunction decreased from moderate preoperatively to none before discharge (P < .001). In‐hospital and 1‐year survival were 93% and 91%, respectively, with 100% survival in the submassive group. No patients developed renal failure requiring hemodialysis at discharge or had a postoperative stroke. Conclusions: In this single institution experience, surgical pulmonary embolectomy is a safe and effective therapy to treat patients with a submassive or massive pulmonary embolism. Although survival in this study is higher than previously reported for patients treated with medical therapy alone, a prospective trial comparing surgical therapy with medical therapy is necessary to further elucidate the role of surgical pulmonary embolectomy in the treatment of pulmonary embolism.

Predictive equations for lung volumes from computed tomography for size matching in pulmonary transplantation

OBJECTIVE Size matching for lung transplantation is widely accomplished using height comparisons between donors and recipients. This gross approximation allows for wide variation in lung size and, potentially, size mismatch. Three-dimensional computed tomography (3D-CT) volumetry comparisons could offer more accurate size matching. Although recipient CT scans are universally available, donor CT scans are rarely performed. Therefore, predicted donor lung volumes could be used for comparison to measured recipient lung volumes, but no such predictive equations exist. We aimed to use 3D-CT volumetry measurements from a normal patient population to generate equations for predicted total lung volume (pTLV), predicted right lung volume (pRLV), and predicted left lung volume (pLLV), for size-matching purposes. METHODS Chest CT scans of 400 normal patients were retrospectively evaluated. 3D-CT volumetry was performed to measure total lung volume, right lung volume, and left lung volume of each patient, and predictive equations were generated. The fitted model was tested in a separate group of 100 patients. The model was externally validated by comparison of total lung volume with total lung capacity from pulmonary function tests in a subset of those patients. RESULTS Age, gender, height, and race were independent predictors of lung volume. In the test group, there were strong linear correlations between predicted and actual lung volumes measured by 3D-CT volumetry for pTLV (r = 0.72), pRLV (r = 0.72), and pLLV (r = 0.69). A strong linear correlation was also observed when comparing pTLV and total lung capacity (r = 0.82). CONCLUSIONS We successfully created a predictive model for pTLV, pRLV, and pLLV. These may serve as reference standards and predict donor lung volume for size matching in lung transplantation.

Venovenous Extracorporeal Membrane Oxygenation With Atrial Septostomy as a Bridge to Lung Transplantation

We report the first successful bridge to lung transplantation using venovenous extracorporeal membrane oxygenation (ECMO) with an atrial septostomy for both pulmonary and right ventricular support. This strategy may provide an alternative to other forms of ECMO support as a bridge to lung transplantation, and potentially allow for ambulation and rehabilitation.

Triage and optimization: A new paradigm in the treatment of massive pulmonary embolism

Background Massive pulmonary embolism (PE) remains a highly fatal condition. Although venoarterial extracorporeal membrane oxygenation (VA‐ECMO) and surgical pulmonary embolectomy in the management of massive PE have been reported previously, the outcomes remain less than ideal. We hypothesized that the institution of a protocolized approach of triage and optimization using VA‐ECMO would result in improved outcomes compared with historical surgical management. Methods All patients with a massive PE referred to the cardiac surgery service between 2010 and 2017 were retrospectively reviewed. Patients were stratified by treatment strategy: historical control versus the protocolized approach. In the historical control group, the primary intervention was surgical pulmonary embolectomy. In the protocol approach group, patients were treated based on an algorithmic approach using VA‐ECMO. The primary outcome was 1‐year survival. Results A total of 56 patients (control, n = 27; protocol, n = 29) were identified. All 27 patients in the historical control group underwent surgical pulmonary embolectomy, whereas 2 of 29 patients in the protocol approach group were deemed appropriate for direct surgical pulmonary embolectomy. The remaining 27 patients were placed on VA‐ECMO. In the protocol approach group, 15 of 29 patients were treated with anticoagulation alone and 14 patients ultimately required surgical pulmonary embolectomy. One‐year survival was significantly lower in the historical control group compared with the protocol approach group (73% vs 96%; P = .02), with no deaths occurring after surgical pulmonary embolectomy in the protocol approach group. Conclusions A protocolized strategy involving the aggressive institution of VA‐ECMO appears to be an effective method to triage and optimize patients with massive PE to recovery or intervention. Implementation of this strategy rather than an aggressive surgical approach may reduce the mortality associated with massive PE.

Utilization of Veno-Arterial Extracorporeal Membrane Oxygenation for Massive Pulmonary Embolism

BACKGROUND The management of massive pulmonary embolism remains challenging, with a considerable mortality rate. Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for massive pulmonary embolism has been reported, its use as salvage therapy has been associated with poor outcomes. We reviewed our experience utilizing an aggressive, protocolized approach of VA-ECMO to triage, optimize, and treat these patients. METHODS All patients with a massive pulmonary embolism who were placed on VA-ECMO, as an initial intervention determined by protocol, were retrospectively reviewed. ECMO support was continued until organ optimization was achieved or neurologic status was determined. At that time, if the thrombus burden resolved, decannulation was performed. If substantial clot burden was still present with evidence of right ventricular (RV) strain, operative therapy was undertaken. RESULTS Twenty patients were identified. Before cannulation, all patients had an RV-to-left ventricular ratio greater than 1.0 and severe RV dysfunction. The median duration of ECMO support was 5.1 days, with significant improvement in end-organ function. Ultimately, 40% received anticoagulation alone, 5% underwent catheter-directed therapy, and 55% underwent surgical pulmonary embolectomy. Care was withdrawn in 1 patient with a prolonged pre-cannulation cardiac arrest after confirmation of neurologic death. In-hospital and 90-day survival was 95%. At discharge, 18 of 19 patients had normal RV function, and 1 patient, who received catheter-directed therapy, had mild dysfunction. CONCLUSIONS VA-ECMO appears to be an effective tool to optimize end-organ function as a bridge to recovery or intervention, with excellent outcomes. This approach may allow clinicians to better triage patients with massive pulmonary embolism to the appropriate therapy on the basis of recovery of RV function, residual thrombus burden, operative risk, and neurologic status.

Veno-Venous Extracorporeal Membrane Oxygenation Use in the Treatment of Bleomycin Pulmonary Toxicity.

Pulmonary toxicity is a devastating complication of bleomycin chemotherapy. This insult is likely exacerbated by the free radical injury induced by high inspired oxygen content, which is required to support these patients. Traditional treatment consists of high-dose corticosteroids. We report the case of a 45-year-old man who developed bleomycin pulmonary toxicity, which failed to respond to treatment with highdose corticosteroids. We used protective mechanical ventilatory settings while supported on veno-venous extracorporeal membrane oxygenation using a bicaval dual-lumen, single cannula system to allow for lung recovery. This case demonstrates the feasibility of using veno-venous extracorporeal membrane oxygenation to treat bleomycin pulmonary toxicity in a patient who has failed traditional therapy.

ABO type and bleeding during adult ECMO

Dear Editor, Serious bleeding occurs in 33–56 % of adult patients on extracorporeal membrane oxygenation (ECMO) and is thought to be in part due to loss of large von Willebrand factor (vWF) multimers [1–3]. In one study of adult ECMO patients, vWF multimers were decreased in 31 of 32 (96.9 %) patients [4]. Patients with type O blood have lower vWF and factor VIII (FVIII) levels [5]. We hypothesized that patients with type O blood would have more bleeding during ECMO. Secondary analysis was performed on an IRB-approved database of adult patients who received ECMO over a 3.5-year period and had detailed information recorded about bleeding as well as ABO type. Patients with clearly identified surgical bleeding were excluded from the analysis. Unfractionated heparin was used for anticoagulation with an activated partial thromboplastin time (aPTT) goal of 60–80 s or activated clotting time (ACT) goal of 180–200 s during VA ECMO and 45–55 s or 160–180 s during VV ECMO. Hemoglobin levels were kept close to 10 g/dL in concert with the Extracorporeal Life Support Organization’s anticoagulation guideline. Patient characteristics, ECMO data, and outcomes were compared between patients with and without type O blood using the Wilcoxon rank sum test or Chi squared test. The primary outcome was serious bleeding, defined as bleeding that required transfusion of at least two red blood cell (RBC) units due to a fall in hemoglobin of 2 g/dL or greater. Multivariable Poisson regression was performed to determine whether RBC transfusion occurred at a higher rate in patients with type O blood after controlling for confounders. Out of 111 patients, 52 (46.8 %) experienced serious bleeding. Patient characteristics, ECMO data, and outcomes are shown in Table 1. There was no difference in the proportion of patients with bleeding by blood type (47.1 % for type O vs. 46.7 % for other, p = 0.97). However, patients with type O blood had more RBC transfusion after controlling for age, total ECMO days, baseline platelet count, baseline international normalized ratio, and the amount of over-anticoagulation during ECMO (adjusted rate ratio for RBC transfusion = 1.47 [95 % CI 1.35–1.60], p < 0.0001. Patients with type O blood were also more likely to be in the top quintile (≥40 RBC units) for RBC transfusion during ECMO (p = 0.02), suggesting more total bleeding per event.

A Novel Large Animal Model of Acute Respiratory Distress Syndrome Induced by Mitochondrial Products.

Objective: We aimed to create a reproducible lung injury model utilizing injection of mitochondrial damage-associated molecular products. Our goal was to characterize the pathophysiologic response to damage-associated molecular pattern mediated organ injury. Summary Background Data: There remain significant gaps in our understanding of acute respiratory distress syndrome, in part due to the lack of clinically applicable animal models of this disease. Animal models of noninfectious, tissue damage-induced lung injury are needed to understand the signals and responses associated with this injury. Methods: Ten pigs (35–45 kg) received an intravenous dose of disrupted mitochondrial products and were followed for 6 hours under general anesthesia. These animals were compared to a control group (n = 5) and a model of lung injury induced by bacterial products (lipopolysaccharide n = 5). Results: Heart rate and temperature were significantly elevated in the mitochondrial product (204 ± 12 and 41 ± 1) and lipopolysaccharide groups (178 ± 18 and 42 ± 0.5) compared with controls (100 ± 13 and 38 ± 0.5) (P <0.05). Lung oxygenation (PaO2/FiO2) was significantly lower 6 hours after injection in the mitochondrial products and lipopolysaccharide groups compared with controls (170 ± 39, 196 ± 27, and 564 ± 75 mm Hg respectively, P = 0.001). Lung injury scoring of histological sections was significantly worse in mitochondrial and lipopolysaccharide groups compared with controls (mitochondrial-64 ± 6, lipopolysaccharide-54 ± 8, control-14 ± 1.5, P= 0.002). Conclusions: Our data demonstrated that the presence of mitochondrial products in the circulation leads to systemic inflammatory response and lung injury. In its acute phase lung injury induced by tissue or bacterial products is clinically indistinguishable.