Anselmo Alonso

Aprotinin and methylprednisolone equally blunt cardiopulmonary bypass–induced inflammation in humans ☆ ☆☆ ★ ★★

Cardiopulmonary bypass induces an inflammatory state characterized by tumor necrosis factor-alpha release. Integrin CD11b is a neutrophil surface adhesive glycoprotein integrin that is rapidly and permanently unregulated by tumor necrosis factor-alpha exposure. The CD11b integrin is known to be the primary neutrophil integrin responsible for neutrophil lung and myocardial entrapment after cardiopulmonary bypass and subsequent reperfusion injury. Twenty-four adults admitted to the hospital for myocardial revascularization were equally randomized to one of three groups: group A (control), group B (methylprednisolone before cardiopulmonary bypass), and group C (low-dose aprotinin protocol). Blood was collected at three times: (1) baseline, (2) 50 minutes of cardiopulmonary bypass duration, and (3) 30 minutes after cardiopulmonary bypass termination. Neutrophil CD11b integrin expression was measured by fluorescence-activated cell sorter analysis and plasma tumor necrosis factor-alpha levels measured by enzyme-linked immunosorbent assay. Group A demonstrated significant (p < 0.05) increases in CD11b expression at times 2 and 3 when results were compared with those of the same group baseline and with those of groups B and C at similar times. No significant changes were noted between groups B and C at any time. Group A demonstrated a significant (p < 0.05) increase in levels of tumor necrosis factor-alpha at time 3 when results were compared with those of the same group baseline and of groups B and C at the same time. No significant changes were noted between B and C at any time. These results demonstrate low-dose aprotinin has a similar antiinflammatory effect to that of methylprednisolone in blunting cardiopulmonary bypass-induced systemic tumor necrosis factor-alpha release and neutrophil integrin CD11b upregulation.

Intrapleural fibrinolytic treatment of multiloculated thoracic empyemas

Acute multiloculated thoracic empyemas incompletely drained by tube thoracostomy alone usually require operation. To avoid a thoracotomy yet treat this difficult problem, intrapleural fibrinolytic agents were employed. Between April 1, 1990, and April 1, 1993, 13 consecutive patients presenting with a fibrinopurulent empyema were demonstrated to have incomplete drainage. To facilitate drainage, streptokinase, 250,000 units in 100 mL 0.9% saline solution (3 patients), or urokinase, 100,000 units in 100 mL 0.9% saline solution (10 patients), was instilled daily into the chest tube, and the tube was clamped for 6 to 12 hours followed by suction. This routine was continued daily for a mean of 6.8 +/- 3.7 days (range, 1 to 14 days) until resolution of the pleural fluid collection was demonstrated by computed chest tomography and clinical indications. This regimen was completely successful in 10 of 13 patients (77%), who had resolution of the empyema, eventual withdrawal of chest tubes, and no recurrence. Two patients, both pediatric liver transplant patients, had an initial good response but eventually required decortication. One patient with a good radiographic response became increasingly febrile during streptokinase therapy and underwent a thoracotomy, but no significant undrained fluid was found. This patients continued fever was believed to be a streptokinase reaction. Urokinase was used subsequently. No treatment-related mortalities or complications occurred. Intrapleural fibrinolytic agents, especially urokinase, are safe, cost-effective means of facilitating complete chest tube drainage, thereby avoiding the morbidity of a major thoracotomy for 77% of a group of multiloculated empyema patients who traditionally would have required open surgical therapy.

Aprotinin reduces interleukin-8 production and lung neutrophil accumulation after cardiopulmonary bypass.

Pulmonary neutrophil entrapment and resultant oxidative injury is thought to be the primary mechanism of cardiopulmonary bypass (CPB) induced lung injury.Interleukin-8 (IL-8), a potent neutrophil chemoattractant induced by cytokines, including tumor necrosis factor-alpha (TNF), is found in increased concentrations in bronchial alveolar lavage fluid (BALF) in lung inflammation. Since aprotinin reduces TNF release during CPB, the effects of aprotinin on BALF IL-8 concentrations and neutrophil levels were determined after CPB in adult humans. Study patients were equally divided into a control group (n = 8, Group 1) and an aprotinin treated group (n = 8, Group 2). In vitro neutrophil chemotaxis was done with volunteer neutrophils using three different chemoattractants: 1) N-formyl-1-methionyl-1-leucyl-1-phenylalanine (FMLP); 2) the supernatant of a human bronchial epithelial cell culture line, A549, after 24 h of TNF stimulation with or without aprotinin or N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) (a potent protease inhibitor), and 3) BALF. Aprotinin treatment significantly (P < 0.05) reduced post-CPB BALF IL-8 concentrations and percentage of neutrophils. In vitro, BALF from Group 1 had significantly greater chemotactic ability when compared with Group 2. The TNF stimulated A549 cell culture supernatant had significantly (P < 0.05) greater chemotactic ability than control supernatant, while aprotinin and TLCK significantly (P < 0.05) reduced this chemotactic ability. These results demonstrate that aprotinin blunts IL-8 production and reduces neutrophil lung accumulation post-CPB. (Anesth Analg 1996;83:696-700)

Glucocorticoids Blunt Neutrophil Cd11b Surface Glycoprotein Upregulation During Cardiopulmonary Bypass in Humans

Neutrophil-endothelial adhesion is the initiating event in neutrophil migration to areas of infection or injury. The binding of neutrophils to endothelium depends upon adhesive glycoproteins, of which the CD11/CD18 glycoproteins are the most important. Because of known upregulation of one of these adhesive glycoproteins (CD11b) during cardiopulmonary bypass (CPB) in humans, we evaluated CD11a, CD11b, and CD11c surface expression before, during, and after CPB in humans, with or without pre-CPB administration of a glucocorticoid (methylprednisolone). Fourteen patients were randomized into two groups: Group S received methylprednisolone (1 g intravenously) 5 min prior to CPB; Group N received no steroid. CD11b was significantly upregulated (P < 0.01) during, and 24 h after, CPB in Group N when compared with controls and Group S at similar time intervals, while in Group S no significant changes were found. Since interleukin-1, tumor necrosis factor, and endotoxin are known to upregulate neutrophil CD11b surface expression and are released during CPB in humans, while steroids are known to suppress the release of these cytokines, the authors conclude that the blunting effect by steroids on CD11b surface expression upregulation during and after CPB in humans is attributed to suppressed cytokine release.

Pulmonary resection for invasive Aspergillus infections in immunocompromised patients.

Standard antifungal medical therapy of invasive pulmonary aspergillosis that occurs in immunocompromised patients with hematologic diseases with neutropenia or in liver transplant recipients results in less than a 5% survival. In view of these dismal mortality rates, we adopted an aggressive approach with resection of the involved area of lung along with systemic antifungal therapy when localized invasive pulmonary aspergillosis developed in these patients. Between January 1987 and December 1993, 14 patients with hematologic diseases and 2 liver transplant recipients underwent resection of acute localized pulmonary masses suggestive of invasive pulmonary aspergillosis a median of 7.5 days (range 1 to 45 days) after the diagnosis was clinically suggested and confirmed by chest computed tomographic scans. Operative procedures done included two pneumonectomies, one bilobectomy with limited thoracoplasty, nine lobectomies, and five wedge resections (one patient with hematologic disease had two procedures). All patients were treated before and after the operation with antifungal agents. Nine (64%) of 14 patients with hematologic disease and 2 (100%) of 2 liver transplant recipients survived the hospitalization with no evidence of recurrent Aspergillus infection after a median 8 months of follow-up (range 3 to 82 months). The five hospital deaths (all patients with hematologic diseases) occurred a median of 20 days after operation from diffuse alveolar hemorrhage in three, graft-versus-host disease in one, and multiple organ system failure with presumed disseminated Aspergillus infection in one. Four of the five deaths were in patients with allogeneic bone marrow transplants. Two of the three patients requiring resection of multiple foci of infection died, as did the only patient who was preoperatively ventilator dependent. In immunocompromised patients with hematologic diseases or liver transplantation with invasive pulmonary aspergillosis, early pulmonary resection should be strongly considered when the characteristic clinical and radiographic pictures appear.

Translocation (X;18) in primary synovial sarcoma of the lung

Primary sarcomas of the lung are extremely rare. Among the most common to occur in this location are leiomyosarcoma, fibrosarcoma, and hemangiopericytoma. Many difficulties are encountered when establishing these sarcoma diagnoses, or one of another pathologic type, because of overlapping histologic features and morphologic similarities between primary and metastatic lesions. In this study, the diagnosis of a primary monophasic synovial sarcoma of the lung was aided by the observation of the X;18 translocation characteristic of this neoplasm. To the best of our knowledge, this is the first cytogenetic report of a primary pulmonary synovial sarcoma.

Pump prime only aprotinin inhibits cardiopulmonary bypass-induced neutrophil CD11b up-regulation.

BACKGROUND The expression of neutrophil integrin CD11b is up-regulated after cardiopulmonary bypass (CPB) and is the neutrophil adhesive molecule of most importance in neutrophil- endothelial adherence. This neutrophil-endothelial adherence is responsible for post-CPB neutrophil-induced reperfusion injury. Low-dose aprotinin protocols inhibit the CPB-induced neutrophil CD11b up-regulation. This investigation was undertaken to evaluate the effects of pump prime only aprotinin (280 mg) on the CPB-induced up-regulation of this neutrophil integrin. METHODS Twenty-two patients scheduled for elective myocardial revascularization were randomized into two groups: (1) control (n = 12), or (2) pump prime only aprotinin (280 mg) (n = 10). Neutrophils were isolated at baseline, 50 minutes of CPB, and 30 minutes after CPB and neutrophil CD11b expression was measured. RESULTS The control group demonstrated a significant (p < 0.05) increase in neutrophil CD11b immunofluorescent staining at 50 minutes of CPB and at 30 minutes after CPB when compared to same group baseline and to the pump prime only aprotinin group at similar time intervals. CONCLUSIONS These results indicate that pump prime only aprotinin modulates the CPB-induced up-regulation of neutrophil CD11b integrin, an important indicator of the systemic inflammatory response to CPB. In addition to blunting of the CPB-induced up-regulation of this neutrophil integrin expression, this pump prime only dose of aprotinin is also reported to be effective at reducing post-CPB bleeding and transfusion requirements. This salutary effect of pump prime only aprotinin suggests that such low-dose regimens can be both therapeutically effective and cost effective.

Cigarette smoking reduces endogenous airway nitric oxide production during cardiopulmonary bypass in humans

C ytokines, including tumor necrosis factor (TNF) and interleukin-lp, are known to increase inducible nitric oxide synthase (iNOS) expression (1,2) with subsequent increased local production of nitric oxide (NO). TNF is among the cytokines known to be systemically released during cardiopulmonary bypass (CPB) in humans (3). Cigarette smoking is known to reduce exhaled NO concentration in humans (4), while smokers are also known to have increased pulmonary complications after CPB (5). Endogenous NO is known to be a bronchodilator (6), and is known to be the nonadrenergic neurotransmitter of bronchodilator nerves in human airways (7). This study was undertaken to evaluate endogenous airway NO production during CPB in a group of currently smoking males, compared to a group who quit smoking at least 30 days but no longer than 6 mo prior to surgery, and a third group who quit smoking more than 6 mo prior to surgery.

Clinical evaluation of a new generation membrane oxygenator: a prospective randomized study

A new generation hollow-fibre membrane oxygenator (Spiral Gold™) has been introduced by Baxter Healthcare (Irvine, CA, USA). The purpose of this study was to evaluate the operational performance of this device under clinical conditions and to compare it to the Univox® Gold™ membrane oxygenator. Following institutional review board approval, and the obtainment of informed consent, 26 patients undergoing coronary artery bypass grafting were randomly assigned to either a Spiral Gold™ (Spiral) (n = 13) or Univox® Gold™ (Univox) (n = 13) group. Study parameters were grouped into the following categories: haematological, haemodynamic, oxygenator performance and perioperative outcomes. All patients received identical surgical, anaesthesia and postoperative care. There were no statistically significant differences in either preoperative or operative parameters between groups. During cardiopulmonary bypass, the Spiral group had a significantly lower pressure drop (26.9 ± 8.2 vs 46.7 ± 16.2 mmHg, p < 0.001). The Spiral group had significantly lower plasma free haemoglobin levels during all time periods of CPB compared to the Univox group. Heat exchange coefficients were higher during the rewarming period in the Spiral patients (0.59 ± 0.28) compared to the Univox group (0.36 ± 0.19), p = 0.06. There were no differences in oxygen transfer between groups, but ventilation gas sweep rates and FiO2 levels were statistically lower in the Spiral group at two of the three sampling time periods. The ratio of ventilating gas sweep rate to blood flow rate was lower in the Spiral group (0.56 ± 0.12) compared to the Univox group (0.74 ± 0.23), p < 0.03. The Spiral Gold™ oxygenator had superior oxygen transfer efficiency and lower haemolysis rates than the Univox® Gold™ oxygenator.

Outcome analysis of coronary artery bypass grafting: minimally invasive versus standard techniques

Minimally invasive coronary artery bypass grafting (MIDCAB) procedures are purported to result in improvements in patient management over standard techniques. A comparative study was performed on risk-stratified patients treated with either technique. Following institutional review board approval, a retrospective random chart review was conducted on 27 MIDCAB and 37 standard coronary artery bypass grafting (CABG) patients who were operated on over a 12-month period at the University of Nebraska Medical Center. Risk stratification was accomplished by dividing the two patient populations, MIDCAB and ‘standard’, into one of four subgroups based on a preoperative risk score. Risk stratification was achieved by dividing the patient populations into one of four subgroups: good, fair, poor and high risk. Both groups received similar operations and surgical interventions, except for the inclusion of cardiopulmonary bypass (CPB). Approximately 200 parameters were collected and analyzed in the following categories: anthropometric, operative and postoperative outcomes. The MIDCAB group had a significantly lower number of vessels bypassed (2.0 ± 0.7 vs 3.4 ± 0.9, p < 0.0001). Total postoperative blood product transfusions trended higher in the standard group (6.1 ± 12.6 U) when compared to the MIDCAB patients (2.3 ± 5.5 U, p < 0.15), although not statistically significant. Postoperative inotrope use was significantly less in the MIDCAB group (19% vs 59%, p < 0.002). Ventilator time in the MIDCAB group was 10.5 ± 5.4 h vs 15.0 ± 12.3 h in the standard group (p < 0.07). The MIDCAB group had an overall greater length of stay, but was only statistically different within the poor-risk subgroup (12.2 ± 10.7 vs 7.5 ± 3.9, p < 0.04). The results of this study show that when CPB is not utilized in treating patients undergoing CABG procedures, the benefits in regards to patient outcomes are unclear. This necessitates the need for further work when comparing outcomes for risk-stratified patients.