Protein C as an Early Marker of Severe Septic Complications in Diffuse Secondary Peritonitis
ABSTRACT To evaluate the predictive value of protein C as a marker of severity in patients with diffuse peritonitis and abdominal sepsis, protein C levels were repeatedly determined and compared with serum levels of antithrombin III, plasminogen, alpha(2)-antiplasmin, Plasminogen activator inhibitor, D-dimer, C1-inhibitor, high molecular weight kininogen, and the C5a, C5b-9 fragments of the complement system. We carried out a prospective study from 44 patients with severe peritonitis confirmed by laparotomy and 15 patients undergoing elective ventral hernia repair who acted as controls. Analyzed biochemical parameters were determined before operations and on days 1, 2, 3, 5, 7, 10, and 14 after operations. For the study group, preoperative average protein C level was significantly lower in the patients who developed septic shock in the late course of the disease, with lethal outcome, than in the patients with severe peritonitis and sepsis who survived (p = 0.0001). In non-survivors, protein C activity remained decreased below 70%, whereas the course of survivors was characterized by increased values that were significantly higher (p < 0.03) at every time point than in those patients who died. Protein C was of excellent predictive value and achieved a sensitivity of 80% and a specificity of 87.5% in discriminating survivors from non-survivors within the first 48 hours of the study (AUC-0.917; p < 0.001), with a "cut-off" level of 66.0%. As for the control group, throughout the study period, protein C activity was permanently maintained within the range of normal, with significant differences with reference to the study group (p < 0.01). These results suggest that protein C represents a sensitive and early marker for the prediction of severe septic complications during diffuse peritonitis, and of outcome.
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ABSTRACT: Sepsis (bloodstream infection) is the leading cause of death in non-surgical intensive care units. It is diagnosed in 750,000 US patients per annum, and has high mortality. Current understanding of sepsis is predominately observational and correlational, with only a partial and incomplete understanding of the physiological dynamics underlying the syndrome. There exists a need for dynamical models of sepsis progression, based upon basic physiologic principles, which could eventually guide hourly treatment decisions. We present an initial mathematical model of sepsis, based on metabolic rate theory that links basic vascular and immunological dynamics. The model includes the rate of vascular circulation, a surrogate for the metabolic rate that is mechanistically associated with disease progression. We use the mass-specific rate of blood circulation (SRBC), a correlate of the body mass index, to build a differential equation model of circulation, infection, organ damage, and recovery. This introduces a vascular component into an infectious disease model that describes the interaction between a pathogen and the adaptive immune system. The model predicts that deviations from normal SRBC correlate with disease progression and adverse outcome. We compare the predictions with population mortality data from cardiovascular disease and cancer and show that deviations from normal SRBC correlate with higher mortality rates.Theoretical Biology and Medical Modelling 02/2006; 3:8. DOI:10.1186/1742-4682-3-8 · 1.27 Impact Factor
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ABSTRACT: Abdominal or pelvic infections in the neonate or adult horse can be diagnosed and treated successfully. Increasing the use of more advanced diagnostic and prognostic tests should improve our early recognition and enable us to monitor the effectiveness of our treatment on an improved level. The use of radionuclide-labeled antimicrobials has the potential to improve the diagnosis of abscesses in the pelvic region or abdomen using a noninvasive method. This technique may also aid in the decision to discontinue therapy. Serum procalcitonin or other inflammatory markers could be used for the prognosis and assessment of horses with diffuse or local intra-abdominal infection. Tests such as these may help veterinarians to assess the effectiveness of the treatment being used through a simple blood assay. Similar tests using umbilical cord blood can also aid in early detection of neonatal infections and enable aggressive early treatment. The standard tenants of maintaining a clean healthy environment to prevent infection and the establishment of drainage or removal of the source of infection as the best treatment still hold true. Surgical drainage or lavage is the recommended therapy for infection and shortens the duration of antibiotic therapy required, which is crucial in this age of antibiotic resistance.The Veterinary clinics of North America. Equine practice 09/2006; 22(2):419-36, ix. DOI:10.1016/j.cveq.2006.04.002 · 1.05 Impact Factor
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ABSTRACT: The decision whether and when to perform a relaparotomy in secondary peritonitis is largely subjective and based on professional experience. No existing scoring system aids in this decisional process. Our aim was to search for variables that could predict positive findings at relaparotomy. Retrospective, clinical study. Tertiary university hospital. Two hundred and nineteen patients of a consecutive series who underwent an emergency laparotomy for secondary peritonitis. None. Sequential prediction models were constructed by accumulation of clinical information in chronological order using logistic regression to determine the strength of association between predictive variables and positive findings at relaparotomy outcome. Positive findings were defined as persistent peritonitis or a new infectious focus at relaparotomy. Relaparotomy (planned or on demand) for secondary peritonitis was performed in 117 of 219 patients (53%), yielding either positive (n=62) or negative (n=55) findings. Discriminatory power for positive findings at relaparotomy improved in the successive (multivariate) models: general patient characteristics (area under the curve, 0.60; 95% confidence interval, 0.52-0.68), adding peritonitis-related variables (area under the curve, 0.73; 95% confidence interval, 0.66-0.80), adding operation-related variables (area under the curve, 0.74; 95% confidence interval, 0.67-0.81), and adding postoperative variables (area under the curve, 0.87; 95% confidence interval, 0.82-0.92). Bootstrap resampling reduced the areas under the curve of the subsequent models only slightly. Sensitivity and specificity of the final model were 82% and 76%, respectively, at a total error rate of 16%. One preoperative predictor and five postoperative predictors significantly increased the need for relaparotomy: younger age, decreased hemoglobin levels, temperature>39 degrees C, lower Pao2/Fio2 ratio, increased heart rate, and increased sodium levels. These data suggest that the causes of secondary peritonitis and findings at emergency laparotomy for peritonitis are poor indicators for whether patients will need a relaparotomy. Factors indicative of progressive or persistent organ failure during early postoperative follow-up are the best indicators for ongoing infection and associated positive findings at relaparotomy.Critical Care Medicine 02/2007; 35(2):468-76. DOI:10.1097/01.CCM.0000253399.03545.2D · 6.15 Impact Factor