Timothy W. Mullett

Acute Allograft Failure in Thoracic Organ Transplantation

Abstract Thoracic organ transplantation is an effective form of treatment for end‐stage heart and lung disease. Despite major advances in the field, transplant patients remain at risk for acute allograft dysfunction, a major cause of early and late mortality. The most common causes of allograft failure include primary graft failure secondary to inadequate heart and lung preservation during cold storage, cellular rejection, and various donor‐recipient‐related factors. During cold storage and early reperfusion, heart and lung allografts are vulnerable to intracellular calcium overload, acidosis, cell swelling, injury mediated by reactive oxygen species, and the inflammatory response. Brain death itself is associated with a reduction in myocardial contractility, and recipient‐related factors such as preexisting pulmonary hypertension can lead to acute right heart failure and the pulmonary reimplantation response. The development of new methods to prevent or treat these various causes of acute graft failure could lead to a marked improvement in short‐ and long‐term survival of patients undergoing thoracic organ transplantation.

Treatment of respiratory syncytial virus pneumonia in a lung transplant recipient: case report and review of the literature.

A 61‐year‐old woman who underwent lung transplantation developed severe respiratory syncytial virus (RSV) pneumonia and experienced respiratory failure requiring mechanical ventilation. She was treated initially with aerosolized ribavirin monotherapy; RSV hyperimmune globulin was later added to her regimen. Lung transplant recipients are acutely susceptible to respiratory infections, including community‐acquired respiratory viruses. Respiratory syncytial virus is particularly difficult to treat in immunocompromised patients because of the lack of proved pharmaceutical agents and solid scientific evidence by which to guide therapy. The most important factor appears to be the early start of therapy; immunocompromised patients who develop RSV pneumonia and subsequent respiratory failure requiring mechanical ventilation have a mortality rate approaching 100%. This case report demonstrates the successful treatment of RSV pneumonia with the combination of aerosolized ribavirin and RSV hyperimmune globulin in a severely ill lung transplant recipient who required mechanical ventilation.

Endobronchial Valves in the Treatment of Persistent Air Leaks

BACKGROUND Endobronchial valves (EBVs) are a useful adjunct in the management algorithm of patients with persistent pulmonary air leaks. They are increasingly used in the management of postsurgical parenchymal air leaks and carry a humanitarian use device exemption for this purpose. We report our experience with EBVs in the management of patients with bronchopleural fistula secondary to postsurgical intervention and spontaneous pneumothorax from medical comorbidities. METHODS An institutional review board-approved retrospective review was conducted of our single-center EBV experience. Patients were categorized as postsurgical versus medical. Data collected included demographic characteristics, indication for and number of valves placed, and chest tube duration before and after valve placement to evaluate overall resolution of air leak. Success was defined as resolution of air leak. RESULTS A total of 14 valve placement procedures were performed. Mean age was 60 years and 10 patients were men. Eight represented prolonged leaks secondary to postsurgical complications and six were secondary to medical comorbidities. Indications for placement of valves in medical patients included persistent leak secondary to lung biopsy, ruptured bleb disease, and pneumothorax after cardiopulmonary resuscitation. Postsurgical indications included leaks secondary to lung biopsy, lobectomy, and ruptured bleb disease. A median of two valves were placed per procedure. A postprocedure median length of stay of 14.5 days was observed in the surgical group compared with 15 days in the medical group. Overall success rate was 57% (surgical group, 62.5%; medical group, 50%). CONCLUSIONS EBVs are a useful adjunct in the management of persistent pulmonary air leaks, particularly when conventional interventions are contraindicated or not ideal. EBVs are well tolerated in the critically ill, have few known complications, are removable, and do not preclude future surgical intervention. Future studies should evaluate EBV efficacy versus the natural course of persistent pulmonary air leaks and their impact on cost and length of stay.

Methemoglobinemia Secondary to Topical Benzocaine Use in a Lung Transplant Patient

OBJECTIVE: To report a case of methemoglobinemia secondary to the administration of topical benzocaine spray in an anemic patient who had previously undergone a lung transplant. CASE SUMMARY: A 40-year-old white man with a past medical history significant for lung transplant acutely decompensated following oropharyngeal administration of topical benzocaine spray. Subsequent blood analysis revealed a methemoglobin concentration of 51.2%. Following the administration of a single dose of methylene blue 2 mg/kg intravenously, the patients respiratory status dramatically improved and stabilized. DISCUSSION: Methemoglobinemia is a rare but potentially fatal condition that may be either acquired or congenital; however, the disorder is most commonly acquired secondary to exposure to oxidizing chemicals, which are often routinely prescribed medications, including benzocaine. Benzocaine can react with hemoglobin to form methemoglobin at a rate that exceeds reduction capabilities, which may result in oxygenation difficulty and respiratory distress. In severe or symptomatic methemoglobinemia, the treatment of choice is methylene blue. CONCLUSIONS: Application of the Naranjo probability scale established a highly probable relationship between topical benzocaine spray and methemoglobinemia and associated respiratory compromise. The risks of palliative use of topical benzocaine in patients with preexisting disorders that compromise oxygen delivery may outweigh any benefit. In our patient, anemia and lung disease increased his risk for clinically significant adverse respiratory events secondary to deficiencies or interferences in oxygen delivery. Topical benzocaine should be administered with caution and careful monitoring in such patient populations.

Identifying Esophagectomy Patients at Risk for Predischarge Versus Postdischarge Venous Thromboembolism

BACKGROUND Current guidelines recommend postoperative venous thromboembolism (VTE) chemoprophylaxis for moderate-risk patients (3% rate or greater) and extended-duration chemoprophylaxis for high-risk patients (6% or greater). Large-scale studies of and recommendations for esophagectomy patients are lacking. This study was designed to evaluate the timing, rates, and predictors of postesophagectomy VTE. METHODS Patients undergoing esophagectomies for cancer were identified from the 2005 to 2012 American College of Surgeons National Surgical Quality Improvement database. Timing and rates of VTE (deep venous thrombosis or pulmonary embolism, or both) were calculated. Events were stratified as predischarge or postdischarge. Perioperative factors associated with 30-day rates of predischarge and postdischarge VTE were analyzed. RESULTS Of 3,208 patients analyzed, the surgical approach was Ivor-Lewis (n = 1,131, 35.3%), transhiatal (n = 945, 29.5%), three-field (n = 587, 18.3%), thoracoabdominal (n = 364, 11.3%), and nongastric conduit reconstruction (n = 181, 5.6%). Rates were 2.0% pulmonary embolism, 3.7% deep venous thrombosis, and 5.1% VTE. Overall median length of stay was 11 days (versus 19 days, p < 0.001, if predischarge VTE). Predischarge VTE occurred on median day 9, whereas postdischarge VTE occurred on day 19 (p < 0.001). Only 17% of VTE occurred after discharge. Multivariate analysis identified being male (odds ratio [OR] 2.09, p = 0.018), white race (OR 1.93, p = 0.004), prolonged ventilation (OR 3.24, p < 0.001), and other major complications (OR 1.90, p = 0.005) as independent predictors of predischarge VTE. Older age (OR 1.06 per year, p = 0.006) and major complications (OR 3.14, p = 0.004) were independently associated with postdischarge VTE. CONCLUSIONS Postesophagectomy VTE occurs in a clinically significant proportion of esophageal cancer patients with identifiable risk factors for predischarge and postdischarge events. Elderly patients and patients with major complications are most likely to benefit from extended-duration chemoprophylaxis.

Survival after Pneumonectomy for Stage III Non-small Cell Lung Cancer

OBJECTIVES Stage III non-small cell lung cancer (NSCLC) has a poor prognosis. Reports suggest that five-year survival after current treatment is between 14 to 24 percent. The purpose of this retrospective study was to investigate the morbidity and mortality of patients diagnosed with stage III NSCLC and treated with pneumonectomy at the University of Kentucky Medical Center in Lexington, KY. METHODS We reviewed the medical record and tumor registry follow-up data on 100 consecutive patients who underwent pneumonectomy for lung cancer at the University of Kentucky. RESULTS We identified thirty-six patients in stage III who underwent pneumonectomy. Ten patients had surgery only, eight patients received adjuvant chemotherapy, and eighteen patients received neoadjuvant therapy. There was one surgical death in this series. Mean follow-up was 2.9 years. One-, three-, and five-year survival was 66%, 38%, and 38%, respectively. Five-year survival for the group with adjuvant therapy was 60%. CONCLUSION Most lung cancer patients present with advanced disease and the prognosis remains poor. Our experience indicates resection offers an above average chance of long-term survival when supplemented with neoadjuvant and/or adjuvant therapy.

Adenosine A2a agonist CGS-21680 improves recovery of ventricular function after ischemia-reperfusion in regionally stunned porcine myocardium

Methods: Open chest pigs underwent 15 minute left anterior descending coronary artery (LAD) ischemia followed by 3.5 hours of reperfusion (RP). Control animals (n 5 6) received 0.9 N NaCl (saline) intracoronary (ic) during RP. Treated animals (n 5 6) received saline for the first 2 hr RP, followed by CGS (0.05–0.1 mg/kg/min, ic) for 1 hour and saline for last 30 minutes. Regional stunning was assessed using sonomicrometry to measure load-insensitive preload recruitable stroke work area (PRSWA).