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  • 1
    ISSN: 1432-1238
    Keywords: Key words Pentoxifylline ; Critically ill ; Sepsis ; Trauma ; Inflammation ; Coagulation ; Platelet function ; Aggregometry ; Collagen ; Epinephrine ; Adenosine diphosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: The methylxanthine derivative pentoxifylline (PTX) is one of those promising substances which are under current investigation to modify or limit inflammatory response. Antiaggregation activity has also been described that may contribute to the beneficial effects of this substance. Long-term effects on platelet function have not been elucidated yet. Design: Prospective, randomized study. Setting: Clinical investigation on a surgical intensive care unit of a university hospital. Patients: 26 trauma patients and 26 patients suffering from sepsis secondary to major operations were consecutively studied. Interventions: The patients prospectively received either 1.5 mg/kg per h pentoxifylline continuously for 5 days (after a loading dose of 600 mg) (trauma-PTX, n=13; sepsis-PTX, n=13) or saline solution as placebo (trauma-control; n=13; sepsis-control, n=13). Measurements: On the day of admission (trauma patients) or day of the diagnosis of sepsis and at 12:00 p.m. during the next 5 days, platelet aggregation induced by adenosine diphosphate (ADP 2.0 μmol/l), collagen (4 μl/ml), and epinephrine (25 μmol/l) was determined by a turbidimetric method from arterial blood samples. Standard coagulation screen was also monitored. Main results: In untreated trauma and sepsis patients, maximum platelet aggregation induced by all three agonists decreased during the first few days after inclusion in the study [trauma: ADP–17.1±8.0 rel% (% change from baseline); sepsis: ADP –26.1±5.6 rel%]. In due course, maximum platelet aggregation recovered, reaching the baseline value or even exceeding it (trauma patients). In the PTX-treated patients, platelet aggregation was significantly less impaired (sepsis group: ADP –4.4±3.3 rel%) or even increased beyond baseline values in the first few days of the study (trauma group: ADP 16.1±8.0 rel%). Fibrinogen plasma levels were lower in the non-treated control groups (p〈0.05) than in the PTX groups. Conclusions: Continuous infusion of PTX for 5 days did not impair platelet function in critically ill patients. In both trauma and sepsis patients, the usual deterioration in platelet function was even attenuated, which may be due to the effects of PTX on cytokine release (e.g., reduction in tumor necrosis factor and interleukin-1), improvement in microcirculation, or additional fibrinolytic effects.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1238
    Keywords: Pentoxifylline ; Critically ill ; Sepsis ; Trauma ; Inflammation ; Coagulation ; Platelet function ; Aggregometry ; Collagen ; Epinephrine ; Adenosine diphosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective The methylxanthine derivative pentoxifylline (PTX) is one of those promising substances which are under current investigation to modify or limit inflammatory response. Antiaggregation activity has also been described that may contribute to the beneficial effects of this substance. Long-term effects on platelet function have not been elucidated yet. Design Prospective, randomized study. Setting Clinical investigation on a surgical intensive care unit of a university hospital. Patients 26 trauma patients and 26 patients suffering from sepsis secondary to major operations were consecutively studied. Interventions The patients prospectively received either 1.5 mg/kg per h pentoxifylline continuously for 5 days (after a loading dose of 600 mg) (trauma-PTX,n=13; sepsis-PTX,n=13) or saline solution as placebo (trauma-control;n=13; sepsis-control,n=13). Measurements On the day of admission (trauma patients) or day of the diagnosis of sepsis and at 12:00 p.m. during the next 5 days, platelet aggregation induced by adenosine diphosphate (ADP 2.0 μmol/l), collagen (4 μl/ml), and epinephrine (25 μmol/l) was determined by a turbidimetric method from arterial blood samples. Standard coagulation screen was also monitored. Main results In untreated trauma and sepsis patients, maximum platelet aggregation induced by all three agonists decreased during the first few days after inclusion in the study [trauma: ADP −17.1±8.0 rel% (% change from baseline); sepsis: ADP −26.1±5.6 rel%]. In due course, maximum platelet aggregation recovered, reaching the baseline value or even exceeding it (trauma patients). In the PTX-treated patients, platelet aggregation was significantly less impaired (sepsis group: ADP −4.4±3.3 rel%) or even increased beyond baseline values in the first few days of the study (trauma group: ADP 16.1±8.0 rel%). Fibrinogen plasma levels were lower in the non-treated control groups (p〈0.05) than in the PTX groups. Conclusions Continuous infusion of PTX for 5 days did not impair platelet function in critically ill patients. In both trauma and sepsis patients, the usual deterioration in platelet function was even attenuated, which may be due to the effects of PTX on cytokine release (e.g., reduction in tumor necrosis factor and interleukin-1), improvement in microcirculation, or additional fibrinolytic effects.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Intensive care medicine 23 (1997), S. 567-573 
    ISSN: 1432-1238
    Keywords: Key words Critically ill ; Sepsis ; Trauma ; Neurosurgery ; Heparin ; Anticoagulation ; Platelet function ; Aggregometry ; Adenosine diphosphate ; Epinephrine ; Collagen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To study the influence of continuous administration of heparin on platelet function in intensive care patients. Design: Prospective, serial investigation. Setting: Clinical investigation on a surgical and neurosurgical intensive care unit in a university hospital. Patients: The study included 45 patients: 15 postoperative with patients sepsis (Acute Physiology and Chronic Health Evaluation II score between 15 and 25), 15 trauma patients (Injury Severity Score 15 to 25), and 15 neurosurgical patients. Interventions: Management of the patients was carried out according to the guidelines for modern intensive care therapy. Sepsis and trauma patients received standard (unfractionated) heparin continuously [aim: an activated partial thromboplastin time (aPTT) approximately 2.0 times normal value; sepsis-heparin and trauma-heparin patients], whereas neurosurgical patients received no heparin (neurosurgical patients). Measurements and results: From arterial blood samples, platelet aggregation was measured by the turbidimetric method. Platelet aggregation was induced by adenosine diphosphate (ADP; 2.0 μmol/l), collagen (10 μg/ml), and epinephrine (25 μmol/l). Measurements were carried out on the day of diagnosis of sepsis or 12 h after hemodynamic stabilization (trauma and neurosurgery patients) (baseline) and during the next 5 days at 12.00 noon. Standard coagulation parameters [platelet count and fibrinogen and antithrombin III (AT III) plasma concentrations] were also monitored. Heparin 4–10 U/kg per h (mean dose: approximately 500 U/h) was necessary to reach an aPTT of about 2.0 times normal. Platelet count was highest in the neurosurgical patients, but it did not decrease after heparin administration to the trauma and sepsis patients. AT III and fibrinogen plasma levels were similar in the three groups of patients. In the sepsis group, platelet aggregation variables decreased significantly (e. g., epinephrine-induced maximum platelet aggregation: − 45 relative % from baseline value). Platelet function recovered during the study and even exceeded baseline values (e. g., ADP-induced maximum platelet aggregation: + 42.5 relative % from baseline value). Continuous heparinization did not blunt this increase of platelet aggregation variables. In the heparinized trauma patients, platelet aggregation variables remained almost stable and were no different to platelet aggregation data in the untreated neurosurgical patients. Conclusions: Continuous administration of heparin with an average dose of approximately 500 U/h did not negatively influence platelet function in the trauma patients. Recovery from reduced platelet function in the sepsis group was not affected by continuous heparinization. Thus, continuous heparinization with this dose appears to be safe with regard to platelet function in the intensive care patient.
    Type of Medium: Electronic Resource
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