Leo M. Gazoni

Does the addition of glutamine to enteral feeds affect patient mortality

Objective:Studies have failed to consistently demonstrate improved survival in intensive care unit (ICU) patients receiving immune-modulating nutrient-enhanced enteral feeds when compared with standard enteral feeds. The objective was to study in a prospective fashion the effects of adding glutamine to standard or immune-modulated (supplemented with omega-3 fatty acids, β-carotene, and amino acids such as glutamine and arginine) tube feeds. Design:Prospective, unblinded study using sequential allocation. Setting:A university surgical trauma ICU. Patients:All surgical and trauma patients admitted to the surgical trauma ICU at a university hospital over a 3-yr period who were to receive enteral feeds (n = 185). Interventions:Sequential assignment to three isocaloric, isonitrogenous diets was performed as follows: standard 1-kcal/mL feeds with added protein (group 1), standard feeds with the addition of 20–40 g/day (0.6 g/kg/day) glutamine (group 2), or an immune-modulated formula with similar addition of glutamine (group 3). The goal for all patients was 25–30 kcal/kg/day and 2 g/kg/day protein. Measurements and Main Results:Patients were followed until discharge from the hospital. The primary end point was in-hospital mortality, and multiple secondary end points were recorded. In-hospital mortality for group 1 was 6.3% (four of 64) vs. 16.9% (ten of 59, p = .09) for group 2 and 16.1% (ten of 62, p = .09) for group 3. After controlling for age and severity of illness, the difference in mortality between patients receiving standard tube feeds and all patients receiving glutamine was not significant (p ≤ .11). There were no statistically significant differences between the groups for secondary end points. Conclusions:The addition of glutamine to standard enteral feeds or to an immunomodulatory formula did not improve outcomes. These findings suggest that enteral glutamine should not be routinely administered to patients with surgical critical illness.

Is Mitral Valve Repair Superior to Replacement in Elderly Patients

BACKGROUND Mitral valve replacement is more frequently performed and perceived to be equivalent to repair in elderly patients, despite the superiority of repair in younger patients. Our objective was to compare mitral repair to replacement in elderly patients age 75 years or older. Patients younger than 75 years undergoing mitral valve surgery served as a reference population. METHODS Consecutive elderly patients undergoing operation for mitral regurgitation at our institution from 1998 to 2006 were reviewed. Elderly patients (mean age, 78.0 +/- 2.8 years) who underwent mitral repair (n = 70) or replacement (n = 47) were compared with cohorts of young patients (mean age, 58.9 +/- 9.3 years) who underwent repair (n = 100) or replacement (n = 98) during the same period. Patient details and outcomes were compared using univariate, multivariate, and Kaplan-Meier analyses. RESULTS Mitral replacement in elderly patients had higher mortality than repair (23.4%, 11 of 47 versus 7.1%, 5 of 70; p = 0.01) or as compared with either operation in the reference group (p < 0.0001). Postoperative stroke was higher in elderly replacement patients compared with repair (12.8%, 6 of 47 versus 0%; p = 0.003) or compared with either young cohort (p = 0.02). Compared with elderly repair patients, elderly replacement patients had more cerebrovascular disease (21.3%, 10 of 47 versus 4.3%, 3 of 70; p = 0.005) and rheumatic mitral valves (21.3%, 10 of 47 versus 0%; p = 0.0001). In the young group, overall complication and mortality were no different between replacement and repair. Long-term survival favored repair over replacement in elderly patients (p = 0.04). One elderly repair patient experienced late recurrence of persistent mitral regurgitation. CONCLUSIONS In patients age 75 years or older, mitral repair is associated with a lower risk of mortality, postoperative stroke, and prolonged intensive care unit and hospital stay compared with mitral replacement. Mitral repair can be performed in preference over replacement even in patients older than the age of 75.

Additive protection against lung ischemia-reperfusion injury by adenosine A2A receptor activation before procurement and during reperfusion

OBJECTIVE Adenosine A2A receptor activation during reperfusion improves lung ischemia-reperfusion injury. In this study we sought to determine whether pretreatment of rabbits with a potent and selective adenosine A2A receptor agonist, ATL-313, before transplantation or whether adding ATL-313 to the preservation solution results in equivalent or additional protection compared with ATL-313 added during reperfusion. METHODS An isolated, ventilated, ex vivo blood-perfused rabbit lung model was used. All groups underwent 2 hours of reperfusion after 18 hours of cold ischemia (4 degrees C). ATL-313 was administered 1 hour before ischemia intravenously, with the preservation solution, and/or during reperfusion. RESULTS Both pretreatment of donor animals with ATL-313 or adding ATL-313 just during reperfusion improved pulmonary function, but significantly greater improvement was observed when pretreatment and treatment during reperfusion were combined (all P < .05). Myeloperoxidase levels, bronchoalveolar lavage tumor necrosis factor alpha levels, and pulmonary edema were all maximally decreased in the combined treatment group. The administration of an equimolar amount of the potent and highly selective adenosine 2A receptor antagonist, ZM 241385, along with ATL-313, resulted in the loss of protection conferred by ATL-313. CONCLUSIONS Adenosine A2A receptor activation with ATL-313 results in the greatest protection against lung ischemia-reperfusion injury when given before ischemia and during reperfusion. Improved pulmonary function observed with adenosine A2A receptor activation was correlated with decreased bronchoalveolar lavage tumor necrosis factor alpha and decreased lung myeloperoxidase. The loss of protection observed with the concurrent administration of the adenosine A2A receptor antagonist, ZM 241385, supports that the mechanism of ATL-313 protection is specifically mediated via adenosine A2A receptor activation.

Activation of A1, A2A, or A3 adenosine receptors attenuates lung ischemia-reperfusion injury

OBJECTIVE Adenosine and the activation of specific adenosine receptors are implicated in the attenuation of inflammation and organ ischemia-reperfusion injury. We hypothesized that activation of A(1), A(2A), or A(3) adenosine receptors would provide protection against lung ischemia-reperfusion injury. METHODS With the use of an isolated, ventilated, blood-perfused rabbit lung model, lungs underwent 18 hours of cold ischemia followed by 2 hours of reperfusion. Lungs were administered vehicle, adenosine, or selective A(1), A(2A), or A(3) receptor agonists (CCPA, ATL-313, or IB-MECA, respectively) alone or with their respective antagonists (DPCPX, ZM241385, or MRS1191) during reperfusion. RESULTS Compared with the vehicle-treated control group, treatment with A(1), A(2A), or A(3) agonists significantly improved function (increased lung compliance and oxygenation and decreased pulmonary artery pressure), decreased neutrophil infiltration by myeloperoxidase activity, decreased edema, and reduced tumor necrosis factor-alpha production. Adenosine treatment was also protective, but not to the level of the agonists. When each agonist was paired with its respective antagonist, all protective effects were blocked. The A(2A) agonist reduced pulmonary artery pressure and myeloperoxidase activity and increased oxygenation to a greater degree than the A(1) or A(3) agonists. CONCLUSION Selective activation of A(1), A(2A), or A(3) adenosine receptors provides significant protection against lung ischemia-reperfusion injury. The decreased elaboration of the potent proinflammatory cytokine tumor necrosis factor-alpha and decreased neutrophil sequestration likely contribute to the overall improvement in pulmonary function. These results provide evidence for the therapeutic potential of specific adenosine receptor agonists in lung transplant recipients.

Thoracic aortic endografting is the treatment of choice for elderly patients with thoracic aortic disease

Objective:To assess the effect of age on outcomes following thoracic aortic endografting. Summary Background Data:Endograft therapy for thoracic aortic disease is rapidly evolving. This therapy is less invasive, and elderly patients with significant medical comorbidities are more frequently referred for endografting. We hypothesized that elderly patients over the age of 75 have worse outcomes after thoracic endografting than patients under the age of 75. Methods:We retrospectively reviewed the charts of the first 42 patients who underwent endografting for thoracic aortic pathology. Charts were reviewed for demographics, comorbid conditions, perioperative complications and death, endoleaks, and results at 3, 6, and 12 months. Preexisting medical conditions were also evaluated to determine if any patient characteristics were associated with adverse outcomes. Perioperative morbidity included cardiac, pulmonary, renal, hemorrhagic, and neurologic (stroke and spinal cord injury) complications. Results:Twenty-four patients were under the age of 75, and 18 patients were 75 or older. Baseline demographics and comorbidities were similar between the 2 groups. There were no differences in operative time, length of stay, perioperative mortality, or the incidence of significant complications between the 2 age groups. Gender, however, was associated with a statistically significant difference between the occurrence of complications, with more women experiencing complications than men (P = 0.026, relative risk = 2.36). One patient (age >75 years) in the entire cohort of 42 (2.4%) suffered a spinal cord injury. At 3 months, endoleaks were more common in the older age group (P = 0.059). Conclusion:Endograft therapy for thoracic aortic disease can be performed safely in elderly patients with no significant increase in perioperative morbidity or mortality compared with younger patients. Female gender is associated with a higher likelihood of perioperative complications, regardless of age. The overall incidence of spinal cord injury is very low. Endograft therapy, when anatomically possible, is the treatment of choice for thoracic aortic disease in elderly patients.

Elective Thoracic Aortic Aneurysm Surgery: Better Outcomes from High-Volume Centers

BACKGROUND Although studies have demonstrated clinical advantages in high-volume (HV) centers performing esophageal and pancreatic resections, thoracic aortic aneurysm repair has not been studied in the same fashion. We sought to determine if HV centers have better outcomes after thoracic aortic aneurysm surgery relative to lower-volume (LV) centers. STUDY DESIGN Retrospective review of prospectively collected data pooled from the 17 institutions participating in the Virginia Cardiac Surgery Quality Initiative (VCSQI) database was performed during a 3-year period. LV centers were those that performed <40 operations during the study period, and HV centers were those that performed >80 operations. Preoperative risk factors and outcomes were compared between the 2 groups. Multivariate analysis was performed to evaluate the impact of center volume on mortality. Only elective operations were studied. RESULTS HV centers performed 515 operations during the study period compared with 216 operations from LV centers. Perioperative mortality was significantly lower in HV centers (3.7%, n = 19) versus LV centers (8.3%, n = 18) (p = 0.02). Incidence of renal failure (HV: 4.5%; LV: 8.3%; p = 0.05) and prolonged ventilator course (HV: 16.7%; LV: 25.5%; p = 0.01) were also lower in the HV centers relative to LV centers. HV centers had higher stroke rates compared with LV centers (HV: 4.8%, LV: 1.4%; p < 0.01). Total hospital cost was

Early adenosine receptor activation ameliorates spinal cord reperfusion injury

42,736 in HV centers and

Inflammatory lung injury after cardiopulmonary bypass is attenuated by adenosine A2A receptor activation

51,296 in LV centers (p = 0.04). On regression analysis, LV centers were significantly associated with increased complications and mortality (all p < 0.05). CONCLUSIONS Although LV centers had lower stroke rates, HV centers had overall better outcomes, lower mortality rates, and considerably lower cost compared with LV centers.

Timing of Stroke After Cardiopulmonary Bypass Determines Mortality

Objectives Adenosine receptor activation at reperfusion has been shown to ameliorate ischemia–reperfusion injury of the spinal cord, but the effects of therapy given in response to ischemic injury are unknown. We hypothesized that adenosine receptor activation with ATL-146e would produce similar protection from ischemic spinal cord injury, whether given at reperfusion or in a delayed fashion. Methods Twenty-two New Zealand white rabbits were divided into three groups. All three groups, including the ischemia–reperfusion group (IR, n = 8), underwent 45 min of infrarenal aortic occlusion. The early treatment group (early, n = 8) received 0.06 μg/kg/min of ATL-146e for 3 h beginning 10 min prior to reperfusion. The delayed treatment group (delayed, n = 6) received ATL-146e starting 1 h after reperfusion. After 48 h, hind limb function was graded using the Tarlov score. Finally, lumbar spinal cord neuronal cytoarchitecture was evaluated. Results Hemodynamic parameters were similar among the groups. Hind limb function at 48 h was significantly better in the early group (3.5 ± 1.0) compared to the IR group (0.625 ± 0.5, P ≤ 0.01). There was a trend towards better hind limb function in the early group compared to the delayed group (2.4 ± 1.1, P = 0.08). Hind limb function was similar between delayed and IR groups. Hematoxylin–eosin spinal cord sections demonstrated preservation of viable motor neurons in the early group compared to the delayed and IR groups. Conclusions Early therapy with ATL-146e provided better protection in this study; therefore, therapy should not be delayed until there is evidence of ischemic neurological deficit. This study suggests that adenosine receptor activation is most effective as a preventive strategy at reperfusion for optimal protection in spinal cord ischemia–reperfusion injury.

Elective Hypothermic Circulatory Arrest to Address Aortic Pathology Is Safe for the Elderly

OBJECTIVE Cardiopulmonary bypass has been shown to exert an inflammatory response within the lung, often resulting in postoperative pulmonary dysfunction. Several studies have shown that adenosine A(2A) receptor activation attenuates lung ischemia-reperfusion injury; however, the effect of adenosine A(2A) receptor activation on cardiopulmonary bypass-induced lung injury has not been studied. We hypothesized that specific adenosine A(2A) receptor activation by ATL313 would attenuate inflammatory lung injury after cardiopulmonary bypass. METHODS Adult male Sprague-Dawley rats were randomly divided into 3 groups: 1) SHAM group (underwent cannulation + heparinization only); 2) CONTROL group (underwent 90 minutes of normothermic cardiopulmonary bypass with normal whole-blood priming solution; and 3) ATL group (underwent 90 minutes of normothermic cardiopulmonary bypass with ATL313 added to the normal priming solution). RESULTS There was significantly less pulmonary edema and lung injury in the ATL group compared with the CONTROL group. The ATL group had significant reductions in bronchoalveolar lavage interleukin-1, interleukin-6, interferon-gamma, and myeloperoxidase levels compared with the CONTROL group. Similarly, lung tissue interleukin-6, tumor necrosis factor-alpha, and interferon-gamma were significantly decreased in the ATL group compared with the CONTROL group. There was no significant difference between the SHAM and ATL groups in the amount of pulmonary edema, lung injury, or levels of proinflammatory cytokines. CONCLUSION The addition of a potent adenosine A(2A) receptor agonist to the normal priming solution before the initiation of cardiopulmonary bypass significantly protects the lung from the inflammatory effects of cardiopulmonary bypass and reduces the amount of lung injury. Adenosine A(2A) receptor agonists could represent a new therapeutic strategy for reducing the potentially devastating consequences of the inflammatory response associated with cardiopulmonary bypass.