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1.
Arch Dis Child Fetal Neonatal Ed ; 94(2): F129-32, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18829617

ABSTRACT

OBJECTIVE: To review the UK neonatal extracorporeal membrane oxygenation (ECMO) service and identify predictors of outcome. DESIGN: Retrospective review of the national cohort. PATIENTS AND INTERVENTIONS: 718 neonates received ECMO for respiratory failure between 1993 and 2005. MEASUREMENTS AND RESULTS: Diagnoses were: 48.0% meconium aspiration syndrome (97.1% survivors), 15.9% congenital diaphragmatic hernia (CDH; 57.9% survivors), 15.9% sepsis (62.3% survivors), 9.5% persistent pulmonary hypertension (79.4% survivors), 5.6% respiratory distress syndrome (92.5% survivors) and 5.1% congenital lung abnormalities (24.3% survivors). The overall survival rate of 79.7% compared favourably with the worldwide Extracorporeal Life Support Organization (ELSO) Registry. Over the period of review, pre-ECMO use of advanced respiratory therapies increased (p<0.001), but ECMO initiation was not delayed (p = 0.61). The use of veno-venous (VV) ECMO increased (p<0.001) and average run time fell (p = 0.004). Patients treated with VV ECMO had a survival rate of 87.7% compared with 73.4% in the veno-arterial (VA) ECMO group; only 42.4% of those needing conversion from VV to VA ECMO survived. In non-CDH neonates, lower birth weight, lower gestational age, older age at ECMO and higher oxygenation index (OI) were associated with increased risk of death. In CDH neonates, lower birth weight and younger age at ECMO were identified as risk factors for death. CONCLUSION: The UK neonatal ECMO service achieves good outcomes and with overall survival rate reaching 80% compares favourably with international results. Advanced respiratory therapies are used widely in UK ECMO patients. Identification of higher OI and older age at ECMO as risk factors in non-CDH neonates reinforces the importance of timely referral for ECMO.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Meconium Aspiration Syndrome/therapy , Respiratory Distress Syndrome, Newborn/therapy , Sepsis/therapy , Female , Hernia, Diaphragmatic/mortality , Hernia, Diaphragmatic/therapy , Humans , Infant, Newborn , Male , Meconium Aspiration Syndrome/mortality , Practice Patterns, Physicians' , Respiratory Distress Syndrome, Newborn/mortality , Retrospective Studies , Risk Assessment , Sepsis/mortality , Survival Rate , Treatment Outcome , United Kingdom/epidemiology
2.
Thorac Cardiovasc Surg ; 54(3): 162-7, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16639676

ABSTRACT

OBJECTIVES: Extracorporeal circulation (ECC) induces platelet activation and inflammation with potentially life-threatening organ dysfunction. Short-acting GP IIb/IIIa inhibitors like tirofiban and eptifibatide protect platelets during ECC without increasing bleeding complications and may reduce inflammation. This study investigates anti-thrombotic and anti-inflammatory effects of different platelet inhibitors. METHODS: Control (untreated) and treated (using either 150 ng/mL tirofiban, 2.5 microg/mL eptifibatide, 0.7 microg/mL milrinone, 15 microg/mL dipyridamol, or 300 KIU/mL aprotinin) heparinized blood of healthy volunteers (n = 6) was recirculated in a well-established ECC model (Chandler loop). Percentage of platelet aggregates, P-selectin-expressing (activated) platelets, CD15-positive aggregates (indicating proinflammatory platelet-granulocyte binding), and platelet counts were determined before (baseline) and after 30 minutes recirculation in unstimulated and ADP-stimulated samples using flow cytometry. Statistical analysis was performed using multifactor ANOVA after transforming the data (logarithms for counts and log odds for percentages). Least square means were backtransformed to obtain appropriate means and their 95 % confidence intervals. Multiple post-hoc comparisons were performed by Tukey's HSD test with a global alpha of 5 %. RESULTS: Significant inhibition was observed for: 1) ECC-induced platelet aggregation by tirofiban (unstimulated: 2.2-fold/stimulated: 2.46-fold), eptifibatide (unstimulated: 1.96-fold/stimulated: 2.65-fold), and milrinone (unstimulated: 1.87-fold/stimulated: 1.37-fold); 2) ECC-induced P-selectin expression by tirofiban (unstimulated: 3.95-fold/stimulated: 2.54-fold), and eptifibatide (unstimulated: 5.87-fold/stimulated: 3.28-fold); 3) ECC-induced platelet loss by tirofiban (1.27-fold), and eptifibatide (1.25-fold); 4) ECC-induced platelet-granulocyte binding by tirofiban (unstimulated: 2.25-fold/stimulated: 1.59-fold), but not by eptifibatide. CONCLUSIONS: Amongst the investigated drugs only GP IIb/IIIa inhibitors decreased activation, aggregation, and loss of platelets during ECC but acted differently on platelet-granulocyte interaction. A short-acting GP IIb/IIIa inhibitor with the potential to inhibit platelet activation and platelet-leukocyte interaction should be considered both for platelet protection and inhibition of platelet-mediated inflammation during ECC.


Subject(s)
Binding, Competitive/drug effects , Blood Platelets/drug effects , Extracorporeal Circulation , Granulocytes/drug effects , Platelet Aggregation Inhibitors/pharmacology , Tyrosine/analogs & derivatives , Aprotinin/pharmacology , Biomarkers/blood , Blood Platelets/metabolism , Dipyridamole/pharmacology , Eptifibatide , Flow Cytometry , Granulocytes/metabolism , Humans , Male , Milrinone/pharmacology , P-Selectin/biosynthesis , P-Selectin/drug effects , Peptides/pharmacology , Phosphodiesterase Inhibitors/pharmacology , Platelet Aggregation/drug effects , Platelet Count , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Serine Proteinase Inhibitors/pharmacology , Tirofiban , Tyrosine/pharmacology
3.
Thorac Cardiovasc Surg ; 53(2): 80-4, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15786005

ABSTRACT

OBJECTIVES: The serine-protease inhibitor aprotinin protects platelet function during cardiopulmonary bypass. However, its safety and efficacy during deep hypothermic circulatory arrest (DHCA) is controversial, and aprotinin is suspected to cause thrombosis especially during hypothermia. The platelet GP IIb/IIIa inhibitor eptifibatide has been assumed to preserve platelet function during cardiopulmonary bypass without increasing bleeding complications. The aim of this study was to compare the effect of aprotinin and eptifibatide on platelet function under conditions of DHCA. METHODS: Heparinized blood from healthy volunteers (n = 10) was incubated in stasis for 30 minutes at 18 degrees C to simulate DHCA and compared to samples incubated at 37 degrees C. The effect of eptifibatide (2.5 microg/ml) and aprotinin (300 KIU/ml) on platelets under these conditions was analyzed by flow cytometry. Platelet aggregates were identified using CD41-antibody binding and size. GPIIb/IIIa function was evaluated with the activation-specific antibody PAC-1 after stimulation with 10 microM ADP. Aggregate numbers and antibody mean-fluorescence are reported as mean +/- standard deviation. RESULTS: Hypothermia induced a 2.5-fold increase of aggregates ( p < 0.001) and a 2.6-fold increase of GPIIb/IIIa activation ( p < 0.001). This effect was not influenced by aprotinin but almost completely inhibited by eptifibatide ( p < 0.001). CONCLUSIONS: Aprotinin has no procoagulatory effect on platelet function during hypothermia but is not protective either. Eptifibatide inhibits hypothermia-induced platelet aggregation in vitro and may prevent aggregate sequestration in the microvasculature and consecutive ischemic organ damage in vivo.


Subject(s)
Aprotinin/pharmacology , Cold Temperature , Peptides/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Blood Platelets/drug effects , Blood Specimen Collection , Eptifibatide , Flow Cytometry , Humans , Hypothermia/blood , In Vitro Techniques , Male
4.
Thorac Cardiovasc Surg ; 52(3): 169-73, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15192778

ABSTRACT

BACKGROUND: Stenoses of the neo-pulmonary artery (NPA) may complicate follow-up of the arterial switch operation (ASO). It is unknown whether the type of patch covering the coronary excision defects ("O"- or "U"-shaped) might influence this complication. METHODS: Echocardiographically and invasively measured NPA pressure-gradients were evaluated retrospectively in 95 children after ASO. Median follow-up was 5.8 years. Defects had been covered with pericardial patches: O/O and U/U (left/right) 34 x each, and 27 x in mixed combinations. The frequency of NPA stenoses requiring re-interventions was registered. RESULTS: Median of the peak instantaneous echocardiographic pressure gradient was 23 mmHg (interquartile range, IQR: 16 - 49, n = 34) in O/O, and 19 mmHg (IQR: 13 - 23, n = 34) in U/U; p < 0.034, t-test. Invasively measured gradients were 49 mmHg (IQR: 17 - 65, n = 12) in O/O, and 12 mmHg (IQR: 7-21, n = 28) in U/U; p < 0.001. One child per O/O- and U/U-group underwent balloon angioplasty of the neo-pulmonary root. Five children of the O/O-group had to undergo repeat surgery, whereas only one child in the U/U-group required repeat surgery ( p < 0.34). CONCLUSIONS: The preferential type of covering the NPA coronary excision sites in ASO should be U-shaped.


Subject(s)
Cardiac Surgical Procedures , Prostheses and Implants , Transposition of Great Vessels/surgery , Anastomosis, Surgical , Angioplasty, Balloon, Coronary , Constriction, Pathologic , Female , Humans , Male , Pulmonary Artery/pathology , Reoperation , Retrospective Studies
5.
Eur J Med Res ; 8(9): 389-96, 2003 Sep 29.
Article in English | MEDLINE | ID: mdl-14555294

ABSTRACT

PURPOSE: The aim of the study was to assess the arterial vascular system of the lower extremities in patients with peripheral arterial occlusive disease using Multislice-CT angiography (MS-CTA) and to compare the results with the standard of reference, intraarterial digital subtraction angiography (IA-DSA). MATERIALS AND METHODS: MS-CTA and IA-DSA of the lower extremities were carried out on 23 patients with peripheral arterial occlusive disease (Fontain Stage IIb: 18, III: 3, IV: 2). MS-CTA comprised a 4 x 2.5 mm collimation, 15 mm table feed/rotation, 0.5 sec rotation time and 3 mm slice thickness (1.5 mm reconstruction increment). Delay time was determined by bolus tracking. 150 ml of contrast media were injected intravenously at a flow rate of 3 ml/sec. Maximum intensity projection (MIP) reformations were performed using a semi-automatic vessel tracking program. MS-CTA (axial and MIP-reformatted images) and IA-DSA were reviewed by two radiologists. The grade of vascular stenosis as well as occlusion were rated on a scale of 0 to 3 (0=0-50% stenosis, 1 = 51-75% stenosis, 2 = 76-99% stenosis, 3 = occlusion). RESULTS: For MS-CTA, the mean delay time was 30.2 s (23-40 s), mean scan time was 37.4 (33-42 s). Data analysis was based upon a total of 1136 vascular segments for both methods (568 each). A comparison of all the evaluated segments in both techniques revealed a MS-CTA / IA-DSA 86.3% match. Out of 442 segments proximal the trifurcation, 386 were correctly assessed in MS-CTA (87.3%) and distal the trifurcation, 101 out of 126 segments were rated correctly (80.2%). In MS-CTA, an overall confidence interval of 95% can be achieved in 83.2% to 89.0% for correctly rated stenosis grading. CONCLUSIONS: In patients with peripheral arterial occlusive disease, MS-CTA of the lower extremity is a promising minimal-invasive method for detection of relevant arterial stenoses. However, the technique was limited to routine diagnostic purposes due to severe calcifications and time consuming reconstruction procedures.


Subject(s)
Angiography/methods , Peripheral Vascular Diseases/diagnostic imaging , Aged , Angiography, Digital Subtraction/methods , Constriction, Pathologic/diagnostic imaging , Female , Humans , Leg/blood supply , Male , Middle Aged , Quality of Health Care , Reproducibility of Results , Sensitivity and Specificity , Tomography, X-Ray Computed/methods
6.
Thorac Cardiovasc Surg ; 51(2): 97-8, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12730819

ABSTRACT

After blunt chest trauma, a patient with chronic coronary heart disease sustained an isolated rupture of the right coronary artery. All findings suggested a heart contusion complicated by a non-compromising pericardial effusion and aggravated by anticoagulation with phenprocoumon. After right-ventricular failure occurred, emergency coronary revascularization could not prevent a fatal outcome. This case emphasizes that a coronary artery lesion may be considered in those cases of thoracic trauma with preexisting coronary calcification.


Subject(s)
Arteries/injuries , Coronary Vessels/injuries , Heart Rupture/etiology , Thoracic Injuries/complications , Wounds, Nonpenetrating/complications , Aged , Coronary Disease/complications , Heart Rupture/diagnosis , Humans , Male , Tomography, X-Ray Computed , Ventricular Dysfunction, Right/complications
10.
Transfusion ; 40(3): 302-5, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10738030

ABSTRACT

BACKGROUND: The safety of fibrin tissue adhesives has been a concern since they entered wide clinical application. Most commercially available kits contain the proteolytic inhibitor, aprotinin, to stabilize the fibrin clot. A bovine protein, this substance has an allergenic potency. CASE REPORT: This case report presents a patient who had a generalized allergic skin reaction, probably triggered by aprotinin upon reexposure to fibrin sealant injected subgaleally to achieve closure of a liquor fistula after neurosurgical treatment. The serologic investigation revealed aprotinin-specific IgE and IgG. From 1990 through 1998, reports of five allergic reactions following 1 million exposures to fibrin sealant were made to the manufacturer. The clinical relevance of allergic reactions to aprotinin contained in fibrin sealants and measures to avoid them are discussed. CONCLUSION: These hypersensitivity reactions are extremely rare (incidence, 0.5/100,000 for all reactions and 0.3/100,000 for serious reactions), but they must be kept in mind as possible adverse events after repeated applications of fibrin sealants within a few weeks.


Subject(s)
Aprotinin/adverse effects , Dermatitis, Atopic/chemically induced , Exanthema/chemically induced , Fibrin Tissue Adhesive/adverse effects , Antibodies, Anti-Idiotypic/blood , Antibody Specificity , Aprotinin/immunology , Enzyme-Linked Immunosorbent Assay , Exanthema/immunology , Female , Fluorescent Antibody Technique , Humans , Immunoenzyme Techniques , Immunoglobulin E/immunology , Middle Aged , Time Factors
11.
Anesth Analg ; 90(2): 262-6, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10648304

ABSTRACT

UNLABELLED: Acute hypersensitivity reactions are serious complications of reexposure to aprotinin. Previous contact via infusions or fibrin tissue adhesives can induce specific antibodies. In this study, we aimed to elucidate the preoperative prevalence of aprotinin-specific antibodies in patients scheduled for cardiac operations. Sera of 520 consecutive cardiosurgical patients were collected preoperatively and screened retrospectively for aprotinin-specific IgG using a standard enzyme-linked immunosorbent assay (ELISA). Positive sera were analyzed also for aprotinin-specific IgA (ELISA) and IgE (fluorescence enzyme immunoassay). The histories of all patients were reviewed with focus on aprotinin preexposure. Of 520 patients, 22 (4%) had specific IgG. Only three of these had a documented aprotinin preexposure. Of 448 patients exposed to aprotinin intraoperatively, 15 had preformed specific antibodies. The only patient presenting with severe anaphylaxis was positive for both IgG and IgE, and had a recent IV preexposure in cardiovascular surgery. The presence of aprotinin-specific IgG alone seems not to induce adverse reactions on exposure. Exposure history alone is not sensitive enough to identify patients with aprotinin-specific antibodies. IMPLICATIONS: Anaphylaxis on IV reexposure to aprotinin is a medical emergency. The clinical significance of preformed aprotinin-specific IgG remains questionable, whereas preformed IgE was present in the only patient who suffered from severe anaphylaxis on reexposure to aprotinin. Preformed antibodies are not reliably predicted by exposure history.


Subject(s)
Anaphylaxis/immunology , Aprotinin/immunology , Cardiac Surgical Procedures , Drug Hypersensitivity/immunology , Hemostatics/immunology , Serine Proteinase Inhibitors/immunology , Aged , Aprotinin/adverse effects , Elective Surgical Procedures , Female , Hemostatics/adverse effects , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Male , Middle Aged , Retrospective Studies , Serine Proteinase Inhibitors/adverse effects
12.
J Thorac Cardiovasc Surg ; 118(2): 348-53, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10425009

ABSTRACT

BACKGROUND: In cardiac operations, aprotinin therapy is used either locally as a component of commercially available fibrin tissue adhesives, intravenously, or combined. Our aim was to examine the formation of aprotinin-specific antibodies with regard to the application mode. METHODS: Sera of 150 patients who had undergone cardiac operations and were receiving aprotinin therapy for the first time were sampled before the operation and at medians of 3.5 and 13.3 months after the operation. Aprotinin-specific IgG including all subgroups and aprotinin-specific IgE were analyzed. Aprotinin was given locally (as contained in fibrin sealant; n = 45; median dose, 6000 KIU), intravenously (n = 46; 2.000 x 10(6) KIU), and combined (n = 59; 2.012 x 10(6) KIU). RESULTS: At 3.5 months, the prevalence of aprotinin-specific IgG antibodies was 33% (15/45 patients) after local, 28% (13/46 patients) after intravenous, and 69% (41/59 patients) after combined exposure (P =.0001). At 13.3 months, the prevalence of aprotinin-specific IgG antibodies was 10% (4/41 patients) after local, 31% (13/42 patients) after intravenous, and 49% (28/57 patients) after combined exposure. Total aprotinin dose was similar in patients who were antibody positive and negative. Before the operation, no aprotinin-specific antibodies were detected. Aprotinin-specific IgE were not found after the operation. CONCLUSION: Local aprotinin contact induces a specific immune response and reinforces that of intravenous exposure. The antibody spectrum is identical to the immune response induced by intravenous exposure. Any exposure should be documented. For use in cardiac operations as a hemostyptic, the necessity itself and alternatives for aprotinin as a stabilizing agent merit consideration.


Subject(s)
Aprotinin/immunology , Fibrin Tissue Adhesive/therapeutic use , Hemostatics/therapeutic use , Immunoglobulin E/analysis , Immunoglobulin G/analysis , Serine Proteinase Inhibitors/immunology , Antibody Formation , Cardiac Surgical Procedures , Drug Therapy, Combination , Enzyme-Linked Immunosorbent Assay , Fibrin Tissue Adhesive/administration & dosage , Fluorescent Antibody Technique , Follow-Up Studies , Heart Diseases/immunology , Heart Diseases/surgery , Hemostatics/administration & dosage , Humans , Injections, Intravenous , Intraoperative Period , Prospective Studies , Treatment Outcome
14.
J Thorac Cardiovasc Surg ; 115(4): 883-9, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9576225

ABSTRACT

OBJECTIVE: Most commercially available fibrin sealants contain aprotinin in doses of 1500 kallikrein inactivator units per milliliter. They are used in many operative disciplines. An elevated risk of hypersensitivity reactions exists at reexposure to aprotinin. Our aim was to examine the immunogenic potency of aprotinin as a fibrin sealant content. METHODS: We investigated 49 children with operatively treated congenital heart disease. All patients received aprotinin only topically as contained in fibrin sealant. Serum samples were drawn preoperatively, 1 week, 2 weeks, 6 weeks, and approximately 1 year after operation. They were analyzed for aprotinin-specific immunoglobulin G antibodies with a standard enzyme-linked immunosorbent assay and a fluorescence enzyme immunoassay for aprotinin-specific immunoglobulin E antibodies. RESULTS: At 1 week, 2 weeks, 6 weeks, and 1 year, we found prevalences of 8% (2 of 26), 8% (2 of 24), 6% (3 of 49), and 0% for aprotinin-specific Immunoglobulin E, and for aprotinin-specific immunoglobulin G 8% (2 of 26), 17% (4 of 24), 39% (19 of 49), and 12% (5 of 41). The doses of aprotinin given did not differ significantly in antibody-negative and antibody-positive patients; no significant factors could predict the immune response. CONCLUSIONS: Our findings show the existence of a subgroup of patients who had aprotinin-specific antibodies develop after topical aprotinin application. Any use of aprotinin must be carefully documented. If aprotinin use is planned in patients who previously underwent a surgical procedure, preexposure to aprotinin in any form must be sought to avoid unexpected anaphylactic reactions. The necessity itself and alternatives for aprotinin as a stabilizing agent in fibrin sealants merit consideration.


Subject(s)
Anaphylaxis/immunology , Aprotinin/immunology , Fibrin Tissue Adhesive/immunology , Heart Defects, Congenital/surgery , Hemostatics/immunology , Immunoglobulin E/immunology , Anaphylaxis/etiology , Aprotinin/adverse effects , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Female , Fibrin Tissue Adhesive/adverse effects , Hemostatics/adverse effects , Humans , Immunoglobulin E/biosynthesis , Infant , Male , Prospective Studies , Risk Factors , Time Factors
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