Sara A. Hennessy

Does reperfusion injury still cause significant mortality after lung transplantation

OBJECTIVES Severe reperfusion injury after lung transplantation has mortality rates approaching 40%. The purpose of this investigation was to identify whether our improved 1-year survival after lung transplantation is related to a change in reperfusion injury. METHODS We reported in March 2000 that early institution of extracorporeal membrane oxygenation can improve lung transplantation survival. The records of consecutive lung transplant recipients from 1990 to March 2000 (early era, n = 136) were compared with those of recipients from March 2000 to August 2006 (current era, n = 155). Reperfusion injury was defined by an oxygenation index of greater than 7 (where oxygenation index = [Percentage inspired oxygen] x [Mean airway pressure]/[Partial pressure of oxygen]). Risk factors for reperfusion injury, treatment of reperfusion injury, and 30-day mortality were compared between eras by using chi(2), Fishers, or Students t tests where appropriate. RESULTS Although the incidence of reperfusion injury did not change between the eras, 30-day mortality after lung transplantation improved from 11.8% in the early era to 3.9% in the current era (P = .003). In patients without reperfusion injury, mortality was low in both eras. Patients with reperfusion injury had less severe reperfusion injury (P = .01) and less mortality in the current era (11.4% vs 38.2%, P = .01). Primary pulmonary hypertension was more common in the early era (10% [14/136] vs 3.2% [5/155], P = .02). Graft ischemic time increased from 223.3 +/- 78.5 to 286.32 +/- 88.3 minutes in the current era (P = .0001). The mortality of patients with reperfusion injury requiring extracorporeal membrane oxygenation improved in the current era (80.0% [8/10] vs 25.0% [3/12], P = .01). CONCLUSION Improved early survival after lung transplantation is due to less severe reperfusion injury, as well as improvements in survival with extracorporeal membrane oxygenation.

Donor factors are associated with bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND Bronchiolitis obliterans syndrome (BOS) is the major hurdle preventing long-term success in lung transplantation, and is the primary reason for the 50% 5-year survival. Recipient and perioperative risk factors have been investigated in BOS, but less is known about donor factors. Therefore, we investigated what donor factors are important in the development of BOS. METHODS We performed a retrospective review of the United Network for Organ Sharing lung transplant database from 1987 to 2008. Lung transplant recipients had yearly follow-up. Donor factors were evaluated for their influence on BOS development. Kaplan-Meier plots of BOS-free survival were compared for each donor factor and a multivariate Cox proportional hazard model for BOS was created with donor factors. RESULTS A total of 17,222 lung transplant recipients were identified; 6,991 recipients had sufficient follow-up BOS data. Of these recipients 57% (n = 3,984) developed BOS within 5 years. Recipients who received lungs from donors who were younger, without an active pulmonary infection, or those without current tobacco use had longer BOS-free survival. Recipients who received lungs with higher partial pressures of oxygen in arterial blood (Pao(2)) developed more BOS (p < 0.0001). Donor high Pao(2), older age, and current tobacco use were independent predictors of BOS in lung transplant recipients. CONCLUSIONS Donor factors and donor management strategies are important contributors to development of recipient BOS. Identification of these factors may help limit BOS and may identify recipients at high risk. Surprisingly, high Pao(2) in the donor is an independent predictor of BOS development.

Geographic Distance Between Donor and Recipient Does Not Influence Outcomes After Lung Transplantation

BACKGROUND The shortage in organ donation is a major limiting factor for patients with end-stage lung disease. Expanding the donor pool would be beneficial. We investigated the importance of geographic distance between the donor and recipient and hypothesized that it would not be a critical determinant of outcomes after lung transplantation. METHODS We retrospectively reviewed the United Network for Organ Sharing lung transplant database from 2000 to 2005 to allow sufficient time for bronchiolitis obliterans syndrome (BOS) development. Allograft recipients were stratified by geographic distance from their donors (local, regional, and national) and had yearly follow-up. The primary end points were the development of BOS and 1-year and 3-year mortality. Posttransplant outcomes were compared using a multivariable Cox proportional hazard model. Kaplan-Meier curves were compared by log-rank test. RESULTS Of 6,055 allograft recipients, donors were local in 59%, regional in 19.3%, and national in 21.7%. BOS-free survival did not differ by geographic distance. Geographic distance did not independently predict BOS (hazard ratio, 1.03; 95% confidence interval, 0.96 to 1.10). Similarly, Kaplan-Meier survival curves were not significantly worse for recipients with national donors. Geographic distance did not independently predict 3-year mortality (hazard ratio, 0.95; 95% confidence interval, 0.89 to 1.01). CONCLUSIONS With appropriate donor selection, moderately long geographic distance (average ischemic time < 6 hours) between the donor and recipient is not associated with the development of BOS or increased death after lung transplantation. By placing less emphasis on distance, more donors could potentially be used to expand the donor pool.

Does urgent or emergent status influence choice in mitral valve operations? An analysis of outcomes from the Virginia Cardiac Surgery Quality Initiative.

BACKGROUND Urgent or emergent status is often associated with increased risk among cardiac operations. The objective of this study was to analyze outcomes and cost differences in patients undergoing elective versus urgent or emergent mitral valve replacement (MVR) and repair operations. METHODS From 2003 to 2008, 1,477 patients underwent isolated, primary mitral valve (MV) operations at 11 different centers in the Commonwealth of Virginia. Patients were stratified into four groups: elective MVR (n = 419), elective MV repair (n = 674), urgent or emergent MVR (n = 261) and urgent or emergent MV repair (n = 123). Preoperative risk, operative features, outcomes, and total costs were evaluated. RESULTS Mitral valve replacement patients had more risk factors, including advanced age. Female sex and severe mitral regurgitation were more common among MV repairs. Mitral valve replacement incurred higher operative mortality (5.2% versus 1.2%; p < 0.001), more major complications (20.6% versus 6.5%; p < 0.001), longer postoperative (10.8 days versus 6.2 days; p < 0.001) and intensive care unit (117.7 hours versus 51.4 hours; p < 0.001) duration, and greater total costs (

Acute Hyperglycemia Abolishes Ischemic Preconditioning by Inhibiting Akt Phosphorylation: Normalizing Blood Glucose before Ischemia Restores Ischemic Preconditioning

45,166 versus

Vancomycin-Associated Nephrotoxicity: The Obesity Factor

26,229; p < 0.001) compared with MV repair operations. Postoperative length of stay was longer for elective MVR patients compared with elective MV repair patients (p < 0.001) as well as for urgent or emergent MVR patients compared with urgent or emergent MV repair patients (p = 0.001). Total hospital costs were also higher for both elective MVR (p < 0.001) and urgent or emergent MVR (p < 0.001) compared with elective MV repair and urgent or emergent MV repair. Risk-adjusted operative mortality (odds ratio, 11.4; p < 0.001) and major complication rates (odds ratio, 7.6; p < 0.001) were highest for urgent or emergent MVR. CONCLUSIONS Mitral valve repair is associated with lower morbidity, mortality, and total costs compared with MVR. For urgent or emergent operations, the improved outcomes with mitral repair versus replacement are even more profound.

Do Polymicrobial Intra-Abdominal Infections Have Worse Outcomes than Monomicrobial Intra-Abdominal Infections?

This study examined the hypothesis that acute hyperglycemia (HG) blocks ischemic preconditioning (IPC) by inhibiting Akt phosphorylation. Brief HG of approximately 400 mg/dL was induced in C57BL/6 mice via intraperitoneal injection of 20% dextrose (2 g/kg). All mice underwent 40 min LAD occlusion and 60 min reperfusion. The IPC protocol was 2 cycles of 5 min ischemia and 5 min reperfusion prior to index ischemia. Results. In control mice, infarct size (IF) was 51.7 ± 2.0 (% risk region). Preconditioning reduced IF by 50% to 25.8 ± 3.2 (P < 0.05 versus control). In HG mice, IF was significantly exacerbated to 58.1 ± 2.3. However, the effect of IPC completely disappeared in HG mice. Normalization of blood glucose with insulin 5 min before IPC recovered the cardioprotective effect. Administration of CCPA before index ischemia mimicked IPC effect. The cardioprotective effect of CCPA, not its chronotropic effect, completely disappeared in HG mice. Phosphorylation of cardiac tissue Akt before index ischemia was enhanced by IPC or CCPA but was significantly inhibited by HG in both groups. Normalization of glucose with insulin reversed the inhibition of Akt phosphorylation by HG. Conclusion. HG abolishes the cardioprotective effect of preconditioning by inhibiting Akt phosphorylation. Normalization of blood glucose with insulin suffices to recover the cardioprotective effect of preconditioning.

Can Nasal Methicillin-Resistant Staphylococcus aureus Screening Be Used to Avoid Empiric Vancomycin Use in Intra-Abdominal Infection?

BACKGROUND Current recommendations suggest that vancomycin dosing utilize actual rather than ideal body weight in obese patients. Thus, obese patients may be at greater risk for nephrotoxicity. The purpose of this study was to compare the incidence of nephrotoxicity in vancomycin-treated obese and lean patients at our institution, where unadjusted, actual body weight-based dosing (capped at 2 g per dose twice daily) is used. We expected obese patients to experience a greater incidence of nephrotoxicity than lean patients. METHODS This study examined a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005-2009 who were not receiving hemodialysis at the time of admission. Patients were stratified by body mass index (BMI; obese ≥30 kg/m(2) vs. lean <30 kg/m(2)). Relative risk (RR), 95% confidence intervals (CIs), and p values were computed using a generalized estimating equation to accommodate a correlated data structure corresponding to multiple episodes of infection per individual. Multivariable analysis was performed. RESULTS A total of 530 patients (207 obese; 323 lean) with 1,007 episodes of infection were treated with vancomycin. Patient demographics, co-morbidities, sites of infection, and infecting organisms were similar in the two groups. Female gender (p=0.042), diabetes mellitus (DM) (p=0.018), and hypertension (HTN) (p=0.0009) were more often associated with obesity, whereas allografts (p=0.022) and peripheral vascular disease (p=0.036) were more often present in lean patients. The Acute Physiology and Chronic Health Evaluation II score >21 was the only variable associated with nephrotoxicity (p=0.039). After adjusting for statistically significant variables, obesity was found not to be associated with a greater risk of nephrotoxicity (RR=0.98; 95% CI=0.93-1.04; p=0.59). CONCLUSION No difference in nephrotoxicity was observed between lean and obese patients treated with vancomycin at our institution.

Bronchiolitis obliterans syndrome occurs earlier in the post―lung allocation score era

BACKGROUND Numerous studies have demonstrated microorganism interaction through signaling molecules, some of which are recognized by other bacterial species. This interspecies synergy can prove detrimental to the human host in polymicrobial infections. We hypothesized that polymicrobial intra-abdominal infections (IAI) have worse outcomes than monomicrobial infections. METHODS Data from the Study to Optimize Peritoneal Infection Therapy (STOP-IT), a prospective, multicenter, randomized controlled trial, were reviewed for all occurrences of IAI having culture results available. Patients in STOP-IT had been randomized to receive four days of antibiotics vs. antibiotics until two days after clinical symptom resolution. Patients with polymicrobial and monomicrobial infections were compared by univariable analysis using the Wilcoxon rank sum, χ(2), and Fisher exact tests. RESULTS Culture results were available for 336 of 518 patients (65%). The durations of antibiotic therapy in polymicrobial (n = 225) and monomicrobial IAI (n = 111) were equal (p = 0.78). Univariable analysis demonstrated similar demographics in the two populations. The 37 patients (11%) with inflammatory bowel disease were more likely to have polymicrobial IAI (p = 0.05). Polymicrobial infections were not associated with a higher risk of surgical site infection, recurrent IAI, or death. CONCLUSION Contrary to our hypothesis, polymicrobial IAI do not have worse outcomes than monomicrobial infections. These results suggest polymicrobial IAI can be treated the same as monomicrobial IAI.

Transplant pneumonectomy in a patient with an acutely thrombosed allograft.

BACKGROUND Vancomycin is used widely as empiric therapy for gram-positive organisms in patients with an intra-abdominal infection (IAI), even in those with no history of methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization. Potential adverse effects of vancomycin include nephrotoxicity, increased cost, and bacterial resistance. We hypothesized that MRSA nasal screening could be used to predict patients with a MRSA IAI and used to avoid unnecessary empiric vancomycin use. METHODS A surgical infections database collected prospectively from a single institution was reviewed for all IAIs between January 1, 2000-December 31, 2011. Patients with and without MRSA obtained from abdominal cultures as either a monomicrobial or polymicrobial isolate were compared by univariate analysis. A multivariable logistic regression was performed to identify independent predictors of MRSA IAI. RESULTS Of 2,591 patients with an IAI, 240 patients had a nasal MRSA screen within 30 d prior to infection and abdominal culture data, with an incidence of 23% for MRSA IAI. Patients with MRSA IAI (n=45) had more healthcare associated infections, lower white blood cell counts and greater rates of positive nasal MRSA screenings compared with those with non-MRSA IAI. By multivariable analysis (C statistic=0.908), the strongest independent predictor of an MRSA IAI was a positive MRSA screen (odds ratio [OR] 40.9, confidence interval [CI] 14.2-118.1). The positive predictive value for a MRSA screen was 53% whereas the negative predictive value of a MRSA screen was 97%. CONCLUSION A negative MRSA nasal screen indicates with near certainty the absence of MRSA as part of an IAI. In the setting of a recent screen, empiric vancomycin can be withheld. Further, rapid MRSA nasal screening could be used to forego or to discontinue vancomycin therapy rapidly in the setting of IAI. This change in empiric antibiotic management of IAI may lead to decreased morbidity, reduction in cost, and a decrease in bacterial resistance.