Sarin causes autonomic imbalance and cardiomyopathy: an important issue for military and civilian health.

Sarin, a lethal chemical nerve agent, may be a causative factor in multifactorial syndrome implicated in the Gulf War and Tokyo terrorist attacks. Although a high dose results in seizure and death, low-dose exposure may lead to autonomic imbalance and chronic cardiac pathologies. In this study, echocardiography and electrocardiography were used to examine the late-onset effects of a low-dose sarin on cardiac structure and function in mice. Adrenal corticosterone and tyrosine hydroxylase mRNA levels were measured. Stress responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis was also tested. Findings demonstrate changes consistent with a dilated cardiomyopathy, including left ventricular dilatation, reduced contractility, and altered electrophysiological and inotropic responses to ß-adrenergic stimulation. Results also indicate reduced adrenal tyrosine hydroxylase mRNA, corticosterone and altered stress responsiveness of HPA indicating autonomic imbalance. The role of low-dose sarin/organophosphate exposure needs to be considered in the military and civilian populations that suffer from autonomic imbalance and/or cardiomyopathies of indeterminate origin.

Evidence for a matrix metalloproteinase induction/activation system in arterial vasculature and decreased synthesis and activity in diabetes.

Pathological remodeling characterized by extracellular matrix (ECM) deposition contributes to the diabetic vascular complications. Matrix metalloproteinases (MMPs) regulate ECM turnover. However, the expression profile of the MMP system in diabetic human tissue remains unknown. The objectives of this study were 1) to identify a local MMP induction/activation system that exists in arterial vasculature and 2) to determine how the MMP system may be altered in diabetes. Internal mammary artery specimens were obtained from patients who did (n = 14) and did not (n = 14) have diabetes and were undergoing coronary artery bypass grafting surgery. ECM inducer protein (EMMPRIN); membrane-type MMP (MT-MMP); and MMP-1, -2, and -9 were quantified by immunoblotting and densitometric scanning (pixels). Pro-MMP-1 and MMP-2 levels were decreased from 952 +/- 120 and 1,081 +/- 508 pixels, respectively, in nondiabetic tissue to 398 +/- 62 and 249 +/- 42 pixels in the diabetic tissue (P < 0.05). Both EMMPRIN and MT-MMP expression and total MMP activity were decreased by twofold in diabetic patients (P < 0.05). These results demonstrated for the first time that an MMP induction and activation system exists in human arterial vasculature and that it is downregulated in diabetes. Decreased MMP activity may contribute to increased collagen deposition and pathological remodeling in diabetes.

Saphenous vein endothelin system expression and activity in African American patients.

OBJECTIVE: Plasma endothelin (ET)-1 levels are significantly higher in African American hypertensive patients than in white hypertensive patients. However, whether the molecular components of vascular ET-1 biosynthesis and function are altered in this population remains to be established. Accordingly, the overall goal of this study was to investigate the effects of race on vascular mRNA and protein levels of ET-converting enzyme (ECE)-1 subisoforms, ET-1, and ET receptor profiles in hypertension. METHODS AND RESULTS: Saphenous vein samples were obtained from African American (n=13) and white (n=15) patients undergoing coronary artery grafting surgery. The expression of preproET-1 and of ECE-1a was upregulated approximately 2- and 3-fold, respectively, in African Americans. In endothelium-intact vessels, the ET(A) expression was higher in whites. In endothelium-denuded vessels, the ET(B) mRNA was 3-fold higher in African Americans, suggesting that vasoconstriction-promoting ET(B) receptors are upregulated in this population. Vascular tissue ET-1 levels and ECE-1 activity were also augmented in African American patients. CONCLUSIONS: This study demonstrated that the biosynthetic pathway of ET-1 is activated to a higher degree and that the ET(B) receptor subtype expression is altered in the peripheral vasculature of African American hypertensive patients. The augmented synthesis and altered expression of ET(B) receptors may both contribute to the increased incidence of hypertension and related complications in this patient population.

Pediatric aortic disruption.

Although trauma is the primary cause of death in children, few reports or series exist regarding the management of traumatic aortic disruption in the pediatric age group. The clinical outcome in children diagnosed with acute aortic disruption may be directly influenced by diagnostic and therapeutic management decisions. We reviewed the clinical course of 3 consecutive pediatric patients (mean age, 10.0 years; range, 4-16 years) admitted to our institution from January 2002 through May 2003 with the diagnosis of acute aortic disruption due to blunt trauma. In each case, the cause was a motor vehicle accident. Major, concomitant injuries involving other organ systems were present in each patient. Our operative goals were to use primary repair techniques, avoid the use of endovascular stent grafts, and use partial left heart bypass during aortic cross-clamping whenever possible. Each patient underwent successful operative repair. Aortic reconstruction techniques included primary suture repair in the 4-year-old patient, patch angioplasty in the 16-year-old, and placement of an interposition conduit in the 10-year-old for a blow-out type aortic injury. All patients received partial left heart bypass during aortic cross-clamping (mean, 36.6 min; range, 27-50 min), via a centrifugal pump, and anticoagulation. All patients recovered without evidence of adverse neurologic sequelae. Operative repair of acute aortic disruption in pediatric patients using circulatory support can provide good outcomes. Although not always feasible, the preferential use of primary aortic repair techniques in lieu of interposition conduits and endovascular aortic stents may decrease the potential for late pseudocoarctation.

Native matrix metalloproteinase characteristics may influence early stenosis of venous versus arterial coronary artery bypass grafting conduits.

PURPOSE: Stenosis and occlusion rates of internal mammary artery (IMA) and saphenous vein (SV) coronary artery bypass grafts (CABGs) are markedly different, which result from respective disparities in vascular remodeling. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate vascular structure and may have important influence on graft patency. However, the MMP milieu and expression profile of the IMA and SV have not been contrasted. Therefore, the aim of this study was to assess and compare the native MMP systems in IMA vs SV conduits. METHODS: IMA (n = 10) and SV (n = 10) specimens were obtained from patients undergoing CABG surgery. Protein levels of MMP-1, MMP-2, and MMP-9, TIMP-1, a membrane-bound MMP activator (MT1-MMP), and an extracellular MMP inducer protein (EMMPRIN) were determined by immunoblotting and quantified by densitometric analysis. MMP-2 and MMP-9 activity was determined by gelatin zymography. RESULTS: MMP-2 levels were significantly higher in SV (2,218 +/- 351 pixels) vs IMA (1,012 +/- 213 pixels) specimens (mean +/- SEM]). There were no significant differences in MMP-1, MMP-9, or TIMP-1 content; however, MT1-MMP and EMMPRIN levels were significantly lower in SV (847 +/- 190 pixels, 1,742 +/- 461 pixels) vs IMA conduits (2,590 + 403 pixels, 5,606 + 678 pixels), respectively (p < 0.05). MMP-9 activity was similar while MMP-2 activity was significantly increased in SV vs IMA specimens. CONCLUSIONS: SV and IMA conduits harbor the same MMP molecular constituents. However, MMP-2 levels and activity are significantly more abundant in the SV compared to the IMA. These differences may contribute to the early pathologic remodeling of the SV vs IMA conduit following CABG surgery.

Downregulation of vascular matrix metalloproteinase inducer and activator proteins in hypertensive patients.

BACKGROUND: Peripheral vasculature undergoes extensive vascular remodeling in the hypertensive state. Regulation of extracellular matrix turnover by the matrix metalloproteinase (MMP) system is an important step in the vascular remodeling process. However, the expression pattern of the vascular MMP system in human hypertension remained unknown. METHODS AND RESULTS: Internal mammary artery specimens were obtained from normotensive (n = 13) and hypertensive (n = 19) patients undergoing coronary artery bypass grafting surgery. Zymographic analysis indicated a threefold decrease in total gelatinolytic activity of MMP-2 and MMP-9 in hypertension. MMP-1 activity was also decreased by fourfold without a significant change in protein levels. Tissue levels of extracellular matrix inducer protein (EMMPRIN), MMP activator protein (MT1-MMP), MMP-1, MMP-2, and MMP-9, as well as tissue inhibitors of MMPs (TIMP-1 and TIMP-2) were assessed by immunoblotting and yielded a significant decrease in MMP-9, EMMPRIN, and MT1-MMP levels in hypertension. In addition, measurement of plasma markers of collagen synthesis (procollagen type I amino-terminal propeptide [PINP]) and collagen degradation (carboxy-terminal telopeptide of collagen type I [ICTP]) indicated no difference in PINP levels but suppressed degradation of collagen in hypertension. Evaluation of profibrotic growth factors demonstrated higher levels of fibroblast growth factor (FGF)-2 in tissue preparations from hypertensive patients but no difference in transforming growth factor-beta1 levels. CONCLUSIONS: These findings demonstrate that not only MMP-1 and MMP-9, but MMP inducer and activator proteins are also downregulated in the hypertensive state. Augmented FGF-2 levels may contribute to parallel decreases in MMP activity and MMP induction system resulting in enhanced collagen deposition in hypertension.

Apico-aortic conduits in children with severe left ventricular outflow tract obstruction.

BACKGROUND: Infrequently, congenital heart defects are complicated by left ventricular outflow tract obstruction (LVOTO) not amenable to conventional reconstruction. Apico-aortic conduits provide a means of palliating such patients until definitive repair is possible. The purpose of this study was to review a single institution's current experience with apico-aortic conduits. METHODS: The medical records of pediatric patients receiving apico-aortic conduits were reviewed. Demographics, operative techniques, preoperative and postoperative physiologic variables, morbidity, mortality, and functional class were recorded. Off-pump and on-pump procedures were categorized for comparison. RESULTS: Ten cases of apico-aortic conduits for left ventricular outflow tract obstruction were identified. Indications included congenital aortic stenosis, aortic atresia, and subaortic stenosis. Six procedures were performed off-pump and four required median sternotomy with cardiopulmonary bypass as necessitated by concomitant procedures. There was one operative death. The remaining patients demonstrated hemodynamic improvements and are all alive to date. One patient required conduit valve replacement. All patients are in New York Heart Association classification I or II at the time of last follow-up. CONCLUSIONS: Apico-aortic conduits provide a safe and effective treatment alternative for select cases of left ventricular outflow tract obstruction. Off-pump techniques are feasible in the majority of cases. This valuable adjunct should be considered whenever conventional repair of left ventricular outflow tract obstruction is considered prohibitive.

Non-blood contacting biventricular support for severe heart failure.

BACKGROUND: Direct mechanical ventricular actuation (DMVA) is a non-blood contacting method of biventricular support. DMVA employs a vacuum attached, pneumatically regulated, flexible membrane to transfer both systolic and diastolic forces to the ventricular myocardium. The purpose of this study was to determine if DMVA effectively restores pump performance when applied to the severely failing heart. METHODS: Bovines (n = 10) underwent thoracotomy and were instrumented for continuous hemodynamic monitoring. Cardiac failure was induced by beta1-blockade to achieve a cardiac index of < 1.5 l/min/m2 for 1 hour. Heart rate was maintained at 100 bpm by atrioventricular sequential pacing. Synchronous DMVA support was then applied for 3 hours. RESULTS: Eight animals achieved significant reductions in cardiac index and mean arterial pressures (35%* and 43%* control, respectively; *p < 0.05). DMVA restored cardiac index to baseline and significantly increased arterial pressures (p < 0.05; DMVA versus cardiac failure). Pulmonary flow and mean pulmonary artery pressures were similar to baseline during DMVA (p = NS). Pathologic exam did not demonstrate evidence of significant device trauma. CONCLUSIONS: DMVA support can effectively restore pump performance of the acutely failing heart. Synchronization may be inherent to the stimulus of cardiac compression. These data further substantiate DMVA's potential as an adjunct to the field of circulatory support.

Gastrointestinal stromal tumor of the posterior mediastinum.

Gastrointestinal stromal tumor (GIST) is a rare, but potentially aggressive tumor. We present an asymptomatic 64-year-old man with an incidental 9-cm GIST that arose in the posterior mediastinum. Wide surgical excision was performed with rotation of an intercostal muscle flap to buttress a surgically created esophageal wall defect. The patient is now free of disease 26 months postoperative. This tumor is defined by the carcinogenic over-expression of KIT-protein, a tyrosine kinase receptor. Accurate diagnosis of gastrointestinal stromal tumor is imperative, as specific medical therapy is now available for potential control of recurrent or metastatic disease.

Surgical versus nonsurgical treatment of empyema thoracis: an outcomes analysis.

BACKGROUND: Empyema thoracis (ET) is associated with substantial morbidity and mortality. The optimal means for draining the pleural space remains controversial but there may be increasing bias for less invasive strategies. This study compared outcome after a nonsurgical versus a surgical approach to ET. METHODS: Patients with ET over a 10-year period (n = 93) were reviewed and stratified into nonsurgical (thoracentesis and/or closed tube thoracostomy) and surgical (thoracotomy, decortication, and/or open window thoracostomy) groups based on pleural drainage techniques. Hospital course was analyzed except when altered by death (n = 12), noncompliance (n = 3), or severe comorbidities (n = 3). RESULTS: Seventy-five patients were stratified into nonsurgical (n = 32) and surgical (n = 43) groups. Demographics, comorbidities, signs and symptoms, and causative organisms were similar between groups. Mortality did not significantly differ in nonsurgical (16%) versus surgical (10%) groups (P = 0.7). Although delay in diagnosis and number of therapeutic interventions were nearly identical, the time to definitive therapy was longer in the surgical versus the nonsurgical group (18 +/- 3.8 versus 8.5 +/- 3.8 days, P = 0.023). The time to discharge after definitive therapy (20.0 +/- 3.5 versus 35.6 +/- 14.0 days, P < 0.001), and overall hospital stay (40.6 +/- 5.3 versus 47.4 +/- 15 days, P = 0.01) was significantly decreased in the surgical versus nonsurgical treatment groups, respectively. CONCLUSION: The treatment of ET is complex. Failure to adequately evacuate the pleural space and/or persistent signs of infection should prompt surgical intervention. Surgical therapy is preferred for advanced stages of ET. Delaying definitive surgical treatment is largely responsible for prolonging hospital course.

Relapse of thrombotic thrombocytopenic purpura associated with decreased VWF cleaving activity.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon syndrome characterized by reversible, systemic aggregation of platelets in the microcirculation and disseminated microvascular thrombosis. Surgery may precipitate TTP and has been associated with relapse in some patients. However, relapse of this life-threatening disorder is unpredictable. We report a patient with an antecedent history of TTP who experienced a relapse after elective cardiac surgery. In this case, decreased von Willebrand factor (vWF)-cleaving metalloproteinase activity and an inhibitor of this endogenous enzyme were demonstrated preoperatively. These findings suggest that decreased vWF-cleaving metalloproteinase activity and/or the presence of its inhibitor may predict an increased risk for surgical-associated relapse of TTP.

Surgical management of esophageal perforation: role of esophageal conservation in delayed perforation.

Definitive repair of esophageal perforation is considered the preferred treatment for patients presenting early (<24 hours). However, the optimal management of delayed presentation (>24 hours) has not been well defined. This study examined the management of esophageal perforation and compared the outcomes of early versus delayed presentation. Records of patients admitted with the diagnosis of esophageal perforation were reviewed. Contrast studies were used to confirm the diagnosis in all cases. Patient demographics and outcome were analyzed to determine differences between early and delayed presentation. A total of 22 cases of esophageal perforation were identified (eight early vs 14 delayed presentations). Operative interventions included primary repair (four), reinforced repair (14) either with intercostal muscle or pleural flap, and a complete esophageal resection (one). Debridement and drainage without repair were done in two patients and a proximal intramural tear was treated with antibiotics and observation. Two patients died during hospitalization. All surviving patients had near-normal restoration of esophageal function. Follow-up at 3 years has shown minimal gastrointestinal problems. One patient required repeat esophageal dilatations and two patients underwent antireflux therapy. Esophageal repair should be considered in all cases of nonmalignant esophageal perforation and should not be influenced by the time of presentation.

Vascular endothelin converting enzyme-1 expression and activity is upregulated in clinical diabetes.

Circulating and vascular endothelin-1 (ET-1) levels are elevated in diabetes, but the molecular components of the enzymatic activation of ET-1 in the vasculature remains unknown. Furthermore, the distribution of ET receptors favors a contractile phenotype in African Americans with diabetes. Whether there is any difference in local ET-1 activation in this population is unknown. This study examined the expression and activity of ET converting enzyme-1 subisoforms (ECE-1) in the internal mammary artery specimens obtained from patients undergoing coronary artery bypass grafting. The study groups included African-American (AA) and Caucasian (CA), nondiabetic (ND) and diabetic (D) patients: AAND N = 10, CAND N = 9, AAD N = 9, and CAD N = 11. The expression of ECE-1 a, ECE-1 b and ECE-1c subisoforms was studied by RT-PCR. ECE-1 a was upregulated 2- and 4-fold in the CAD and MD groups, respectively (P < .05). In African-American patient groups, ECE-1 activity (fmol/ mg protein.h) was augmented from 2,804 +/- 185 in nondiabetic tissue samples to 6,857 +/- 393 in the diabetic tissue (P < .05). There was a similar increase in the CAD group, which did not significantly differ from AA diabetics. ECE-1 inhibitors, phosphoramidon and FR-901533, inhibited vascular ECE-1 activity by more than 80%. While neutral endopeptidase (NEP) and matrix metalloproteinase-2 (MMP-2) are able to process big ET-1, inhibitors of NEP (thiorphan) and MMP (batimistat) did not affect ECE-1 activity. In conclusion, the enzymatic pathway essential for generating vascular ET-1 is activated in the vasculature of both AA and CA diabetic patients and this activation is highly specific for ECE-1.

Decreased vascular matrix metalloproteinase abundance in diabetic patients with symptomatic macroangiopathy.

The incidence of diabetic amputations is 2- to 3-fold higher in African-American patients compared to Caucasians. Vascular remodeling characterized by extracellular matrix (ECM) deposition occurs in diabetes and contributes to vascular complications. The matrix metalloproteinases (MMP) play important roles in the regulation of collagen turnover and vascular remodeling. However, the temporal expression profile of MMPs in diabetic vascular tissue during the disease process remained unknown. The objective of this study was to compare the vascular MMP system in African-American diabetic patients without symptoms to patients undergoing lower limb amputation due to severe vascular complications. Internal mammary artery (IMA, N = 8) and anterior/posterior tibial artery (AT/PT, N = 8) specimens were obtained from patients undergoing coronary artery bypass grafting and lower limb amputation, respectively. ECM inducer protein (EMMPRIN) and MMP activator membrane-type MMP (MT1-MMP), as well as MMP-1, -2, and -9, were quantified by immunoblotting and densitometry (pixels). MMP-1 and -9 levels were decreased from 398 +/- 61 and 175 +/- 54 pixels, respectively, in IMA tissue to 287 +/- 31 and 51 +/- 36 pixels in the AT/PT tissue (P < .05). Both EMMPRIN and MT1-MMP expression was increased by 3-fold in AT/PT preparations (P < .05). These results provided evidence that the molecular components required for the induction and activation of the MMP system exist in arterial vasculature and, MMP expression is downregulated in diabetic patients with severe complications despite elevated MMP inducer and activator proteins. Decreased MMP activity may contribute to pathological remodeling leading to increased incidence of amputations in African-American patients.

Cardiac function after acute support with direct mechanical ventricular actuation in chronic heart failure.

Direct mechanical ventricular actuation (DMVA) exerts direct cardiac compression/decompression and does not require blood contact. The safety and effects of DMVA support in chronically dysfunctional beating hearts in vivo have not been established. This study evaluated hemodynamics and load-independent systolic/diastolic cardiac function before/after acute support (2 hours) using DMVA in small hearts with induced chronic failure. Chronic heart failure was created in seven small dogs (15 ± 2 kg) via either serial coronary microembolizations or right-ventricular overdrive pacing. Dogs were instrumented to measure cardiac output, hemodynamic pressures, left ventricular volumes for pressure-volume analysis via preload reduction. Temporary cardiac support using a DMVA device was instituted for 2 hours. Hemodynamic and mechanical assessments, including dobutamine dose-responses, were compared both before and after support. Hemodynamic indices were preserved with support. Both left-ventricular systolic and diastolic function were improved postsupport, as the slopes of the preload-recruitable stroke work (+29 ± 7%, p < 0.05) and the end-diastolic pressure-volume relationship (EDPVR: -28 ± 9%, p < 0.05) improved post-DMVA support. Diastolic/systolic myocardial reserve, as assessed by responsiveness to dobutamine challenges, was preserved after DMVA support. Short-term DMVA support can safely and effectively sustain hemodynamics, whereas triggering favorable effects on cardiac function in the setting of chronic heart failure. In particular, DMVA support preserved load-independent diastolic function and reserve.

Enhanced angiotensin II-induced cardiac and aortic remodeling in ACE2 knockout mice.

Angiotensin-converting enzyme 2 (ACE2) is present in the heart and thought to exert protective functions. We conducted studies in ACE2 deficient mice to determine whether enzyme loss would exacerbate the cardiac and vascular pathological responses to chronic subcutaneous (sc) angiotensin II (Ang II) infusion. Eight-week-old male ACE2 knockout (KO) and wild type (WT) mice were infused with Ang II (1000 ng/kg per min, 4 weeks) using mini-osmotic pumps. Blood pressure (radiotelemetry), cardiac function (echocardiography, echo), cardiac/aortic structure (histology, collagen, and oxidative stress), and vascular inflammation were examined. Before Ang II infusion, ACE2 KO mice showed unaltered cardiac function and blood pressure. After 4 weeks of Ang II infusion, the mean arterial pressure (MAP) increased from 96 ± 2 to 136 ± 17 mm Hg (∼40%) in WT and from 104 ± 5 to 141 ± 13 mm Hg (∼ 35%) in ACE2 KO. While there were no differences in MAP between groups, the ACE2 KO responded differently to the hypertensive stimulus. Echo analysis revealed severe myocardial dysfunction in Ang II-infused ACE2 KO (Ang ACE2 KO). Ejection fraction was lower (39% versus 50%) as was fractional shortening (27% versus 38%) in ACE2 KO versus WT, respectively. Cardiac dysfunction was associated with hypertrophic cardiomyopathy shown by increased left-ventricular wall thickness, average cardiomyocyte cross-sectional area, and heart weight/body weight ratio. Collagen staining in the myocardium and aorta revealed increased collagen in Ang ACE2 KO, suggestive of remodeling. Results also showed enhanced oxidative stress in the myocardium and aorta of Ang ACE2 KO. There was a 3-fold elevation in macrophage inflammatory protein 1α (MIP 1α) in the aorta of ACE2 KO. Studies in the ACE2 KO model reveal the importance of ACE2 in the maladaptive cardiac and aortic responses to Ang II stimulation, seen as enhanced remodeling using physiological, structural, and biochemical markers. Results document a cardio- and vascular-protective role of ACE2 under pathological conditions.

Ventricular actuation improves systolic and diastolic myocardial function in the small failing heart.

BACKGROUND: Direct mechanical ventricular actuation (DMVA) provides non-blood contacting augmentation of ventricular function. The device has promise for supporting the pediatric heart. The purpose of this study was to assess DMVA's effect in a small animal model of heart failure. METHODS: Anesthetized rabbits (n = 6) underwent sternotomy and were instrumented for hemodynamic monitoring. A 10-MHz ultrasound probe was used for transesophageal echocardiography imaging. Heart failure (cardiac output <50% baseline) was induced with esmolol. Phenylephrine was titrated to maintain baseline mean arterial pressure. Transesophageal echocardiography imaging was acquired at baseline, heart failure, and subsequent DMVA support for 2 hours. Image analysis was used to derive ejection fraction, cardiac output, and stroke work as measures of left ventricular function. Speckle tracking software was used to derive myocardial strain rates as load-independent measures of left ventricular myocardial function. RESULTS: Mean ejection fraction was significantly increased during DMVA support (0.585 +/- 0.035) versus failure (0.215 +/- 0.014; p < 0.001). Peak global left ventricular systolic and diastolic strain rates (1/second) were significantly increased during DMVA (-2.85 +/- 0.33 and 2.92 +/- 0.37) versus failure (-1.69 +/- 0.11 and 1.99 +/- 0.14; p < 0.001 and 0.004, respectively). Peak strain rates during DMVA in the failing heart were similar to baseline. CONCLUSIONS: Direct mechanical ventricular actuation augments both systolic and diastolic left ventricular pump function. Diastolic augmentation distinguishes the device from other direct cardiac compression methods. This study demonstrated that DMVA in the small-sized, failing heart improves both systolic and diastolic myocardial function, which has favorable implications for left ventricular recovery. Direct mechanical ventricular actuation's salutary effects can be provided to the failing pediatric heart without complications of blood contact.

Choice of first intervention is related to outcomes in the management of empyema.

BACKGROUND: The study determined whether the first procedure; simple drainage (tube thoracostomy, pigtail catheter) or operation (video-assisted thoracic surgery [VATS], thoracotomy) was related to outcomes in the management of empyema. METHODS: Data were collected from 104 consecutive patients with empyema. Primary outcomes were additional procedures and death. Predictor variables included age, delay, Karnofsky performance status (KPS), Charlson comorbidity index (CCI), serum albumin, malignancy, Acute Physiology and Chronic Health Evaluation II score, loculations on computed tomography scan, empyema stage, and first procedure choice. RESULTS: Advanced empyema (> or = stage IIA) was present in 84% of patients. Overall treatment success rates (no death, no additional drainage procedures) among evaluable patients for pigtail drainage, tube thoracostomy, VATS, and thoracotomy were 40% (4 of 10), 38% (14 of 37), 81% (13 of 16), and 89% (32 of 36), respectively. Five patients underwent miscellaneous procedures. Univariate variables associated with hospital death included KPS, CCI, and drainage as the first procedure. In multivariate analyses, KPS (coefficient, -0.06, p = 0.002) and failure of the first procedure (odds ratio [OR], 6.76; 95% confidence interval [CI], 1.45 to 31.4, p = .01) were independent predictors of death. Simple drainage as the first procedure was a strong, independent predictor of failure of the first procedure (OR, 11.1; 95% CI, 3.51 to 34.9; p = .00004). CONCLUSIONS: The choice of the first procedure is critical in the outcome for treatment of empyema, even with adjustment for confounding variables. VATS or thoracotomy as initial therapy for advanced empyema is associated with better outcomes.