Predictive relevance of clinical scores and inflammatory parameters in secondary peritonitis.

HYPOTHESIS: To measure and evaluate clinical scores and various inflammation parameters for providing a better outcome assessment of patients with secondary peritonitis. DESIGN: Prospective study. SETTING: ICU of a university and a university affiliated hospital. PATIENTS: Fifty-six patients with severe secondary peritonitis were enrolled in this study executed within 4 years. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken preoperatively and 2, 6, 8, 12, 18, 24, 30, 36, 42 and 48 hours post operation, thereafter every 12th hour until day 5 respectively once daily until day 14. Etiology of peritonitis, clinical score systems (APACHE II, MOF and SOFA), and 27 mainly with activity tests or enzyme-immunoassays measurable inflammation parameters were simultaneously analyzed and stratified into lethal outcome (n = 11) or survival (n = 45), respectively. The etiological distribution of peritonitis was identical among both groups. Proportion of intraperitoneal fungi, E. coli, and bacteroids was substantially higher during the primary operation in the group with lethal outcome. With increasing significance initial and follow-up APACHE II, MOF and SOFA scores provided higher values in this group. Various plasma/serum parameters of hemostasis, leukocyte proteolytic system, acute phase reaction, cytokine system, cell adhesion, opsonization, and main organ functions showed significantly different values between both groups at the preoperative stage and/or during observation period I (day 0-4). Logistic regression analysis revealed the SOFA score and neopterin concentration as the combination with the best sensitivity (63.6%) and specificity (93.2%) for predicting the patients' survival even at the preoperative stage. For the observation period I, the combination of SOFA score and TNF receptor II showed the highest predictive sensitivity (72.7%) and specificity (95.6%). CONCLUSION: Evaluation of the severity of secondary peritonitis using a scoring system with high prognostic relevance could conceivably result in an earlier and adequate application of intensive care such as hemofiltration, administration of immunoglobulins and serial abdominal lavage to improve successful outcome.

Significance of Elecsys S100 immunoassay for real-time assessment of traumatic brain damage in multiple trauma patients.

BACKGROUND: The neuroprotein S100 released into the circulation has been suggested as a reliable marker for primary brain damage. However, safe identification of relevant traumatic brain injury (TBI) may possibly be hampered by S100 release from peripheral tissue. The objective of this study was to measure early S100 levels using the Elecsys S100 immunoassay for real-time assessment of severe TBI in multiple trauma. METHODS: Consecutively admitted multiple trauma patients (injury severity score >or=16 points) were stratified according to the results of the initial cerebral computed tomography (CCT) examination. S100 serum levels were determined at admission and at 6, 12, 24, 48 and 72 h after trauma. Data were correlated to creatine phosphokinase (CK) and lactate dehydrogenase (LDH) serum levels. Using receiver operating characteristic (ROC) analysis, the discriminating power of S100 measurement was calculated for the detection of CCT+ findings. RESULTS: Median S100 levels of CCT+ patients (n=9; 37 years) decreased from 3.30 microg/L at admission to 0.41 microg/L 72 h after trauma. They revealed no significant differences to CCT- patients (n=18; 44 years), but remained elevated compared to controls. Median CK and LDH levels correlated with the corresponding S100 levels during the first 24 h after trauma. ROC analysis displayed a maximum area under the curve of only 0.653 at 12 h after trauma. No significant difference was calculated for the differentiation between CCT+ and CCT- patients. CONCLUSIONS: Measurements of S100 serum levels using the Elecsys S100 immunoassay are not reliable for the real-time detection of severe TBI in multiple trauma patients. Due to soft tissue trauma or bone fractures, S100 is mainly released from peripheral sources such as adipocytes or skeletal muscle cells.

Rapid measurement of S-100B serum protein levels by Elecsys S100 immunoassay in patients undergoing carotid artery stenting or endarterectomy.

OBJECTIVES: This study was designed to apply the rapid Elecsys S100 immunoassay for real-time measurement of S100 protein serum levels indicating acute brain damage in patients undergoing carotid artery stenting (CAS) or endarterectomy (CEA). DESIGN AND METHODS: Data of 14 CAS patients were compared to those of 43 CEA and 14 control patients undergoing coronary angiography (CA). S100 serum levels were measured by the full-automatic Elecsys S100 immunoassay and compared to those obtained by the well-established LIA-mat S100 system. RESULTS: In contrast to CAS and CA patients, median S100 serum levels of CEA patients significantly increased to 0.24 ng/mL before declamping, but subsequently returned to baseline. Three CEA patients with neurological deficits showed sustained elevated S100 levels 6 h after extubation. Absolute S100 values were not significantly different between the two methods. Bland-Altman plot analyses displayed a good agreement, mostly indicating slightly smaller values applying the Elecsys S100 system. CONCLUSIONS: The Elecsys S100 system appears to be suitable for rapid real-time detection of neurological deficits in patients undergoing CAS and CEA. Persistent elevations of Elecsys S100 levels during CEA were associated with prolonged neurological disorders, whereas transient increases seem to represent impaired blood-brain barrier integrity without neurological deficits.

An enzyme-linked immunosorbent assay for human cathepsin X, a potential new inflammatory marker.

The human lysosomal cysteine-type carboxypeptidase cathepsin X is mainly present in monocytes and macrophages and may be released into the circulation due to constitutive and/or regulated secretion by (activated) immune cells. To define its potential diagnostic value as an inflammatory marker, we have developed a highly sensitive and specific sandwich-type immunoassay (ELISA) for cathepsin X permitting both intra- and extracellular detection and quantification. The dynamic range of the cathepsin X ELISA was determined to be 100 (detection limit) to 8000 pg/ml. Reproducibility of both within and between runs yielded coefficients of variation (CVs) of 2.7-3.5% and 6.3-7.3%, respectively. Cross-reactivity with other members (cathepsin B, L) of the thiol-dependent cathepsin family was not observed. The ELISA was used to quantify cathepsin X in leukocytes as well as in plasma of healthy volunteers and patients with multiple trauma. During the first 72 h after trauma, plasma levels of cathepsin X increased significantly, particularly in patients who died during the posttraumatic period. In comparison to the well-known inflammation marker neutrophil elastase, cathepsin X levels predicted survival with a higher significance in the later posttraumatic phase. In conclusion, this report provides the first evidence of cathepsin X immunoreactivity not only in cell lysates but also in plasma samples. We suggest that the newly developed highly reproducible ELISA will be of great value for further evaluation of this protease as a diagnostic and/or prognostic marker in inflammatory diseases.

Bilateral lavage with diluted surfactant improves lung function after unilateral lung contusion in pigs.

OBJECTIVE: This study evaluates the effects of bronchoalveolar lavage with diluted surfactant on unilateral lung contusion-induced lung dysfunction. DESIGN: Randomized prospective animal study. SETTING: An animal laboratory. SUBJECTS: Twenty adult pigs, weighing 25-35 kg. INTERVENTIONS: Animals were randomly assigned to controls and surfactant treatment. Bilateral lavage with surfactant treatment began 30 mins after unilateral lung contusion. Then 25 mg/kg of body weight diluted Curosurf (5 mg/mL) was applied in a volume of 5 mL/kg of body weight. Observation time was 8 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: The Pao2/Fio2 ratio fell from 500 to 250 and then recovered gradually in controls and surfactant-treated pigs. After another 4 hrs, the Pao2/Fio2 ratio deteriorated again in controls, but not in surfactant-treated animals. Total compliance fell by 50% after injury but was completely restored by surfactant treatment. Lung contusion increased the median number of neutrophils in bronchoalveolar lavage fluid from 2% to 30% of total cells and peaked >60% at 480 mins in the contused lungs of control pigs. Surfactant-treated pigs had 40% neutrophils at 480 mins without reaching significant difference to controls. The leukocyte neutral proteinase inhibitor increased to 500 ng/mL at 30 mins postinjury in the contused lungs and increased to 2000 ng/mL after surfactant treatment. CONCLUSIONS: Bilateral bronchoalveolar lavage with diluted surfactant can effectively improve lung function after experimental unilateral lung contusion in pigs.

The prognostic value of polymorphonuclear leukocyte elastase in patients with primary breast cancer.

A variety of serine proteases, including urokinase-type plasminogen activator (uPA), plasmin,and polymorphonuclear leukocyte elastase (PMN-E), have been implicated in the processes of tumor cell invasion and metastasis. Besides degrading of matrix proteins, PMN-E has been shown to be able to cleave and inactivate plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of uPA, and alpha2-antiplasmin, the natural inhibitor of plasmin, thus enabling an uncontrolled matrix degradation by the fibrinolytic enzymes. Because only limited data are available on a relationship between the tumor level of PMN-E and prognosis in primary breast cancer patients, in the present study we have measured with an ELISA the levels of PMN-E (in complex with alpha1-proteinase inhibitor) in cytosolic extracts of 1143 primary breast tumors. Levels of complexed PMN-E have been correlated with the lengths of metastasis-free survival (MFS), relapse-free survival, and overall survival, and a comparison was made with data previously obtained for uPA and PAI-1. Our results show that patients with a high PMN-E level in their primary tumor had a rapid relapse and an early death compared with patients with a low tumor level of PMN-E. This held true for node-negative and node-positive subgroups of patients as well. The relationship of PMN-E with a poor prognosis was especially obvious during short-term follow-up (0-60 months). In Cox multivariate regression analysis, corrected for the traditional prognostic factors, PMN-E was an independent prognostic factor, and high levels of PMN-E were associated with a poor MFS [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.23-2.16; P < 0.001], relapse-free survival (HR, 1.45; 95% CI, 1.10-1.89; P = 0.01), and overall survival (HR, 1.64; 95% CI, 1.20-2.23; P = 0.003). Furthermore, in all three multivariate models, PMN-E still added significantly to the model after the additional inclusion of the uPA. PMN-E was an independent prognostic factor for MFS even in the multivariate analysis including the traditional clinical prognostic factors and the strong established biochemical prognostic factors uPA and PAI-1. Our present study suggests that PMN-E is associated with breast cancer metastasis, and knowledge of the tumor PMN-E status might be helpful in selecting the appropriate individualized (adjuvant) treatment for patients with breast cancer.

Serum S-100B and interleukin-8 as predictive markers for comparative neurologic outcome analysis of patients after cardiac arrest and severe traumatic brain injury.

OBJECTIVE: To compare S-100B and interleukin-8 serum values on scene/at admission and 12 hrs later with respect to neurologic long-term outcome 12 months after cardiac arrest and return of spontaneous circulation, as well as after severe traumatic brain injury. DESIGN: Prospective comparative cohort study. SETTING: On scene; intensive care units of a university hospital. PATIENTS: Twenty patients with out-of-hospital cardiac arrest. Twenty patients with severe traumatic brain injury. INTERVENTIONS: Therapy was adjusted to the standards of modern prehospital and intensive care management by physicians who were not involved in the study. MEASUREMENTS AND MAIN RESULTS: First median S-100B values of the cardiac arrest group (4.42 ng/mL) mounted as high as those of the traumatic brain injury group (4.11 ng/mL). Within 12 hrs, S-100B levels significantly decreased to 0.75 ng/mL in cardiac arrest patients and to 0.68 ng/mL in traumatic brain injury patients but remained significantly elevated compared with the controls (0.04 ng/mL). Interleukin-8 levels of the cardiac arrest patients on scene (30.33 pg/mL) were clearly elevated above normal (12.60 pg/mL) and increased significantly to 101.40 pg/mL after 12 hrs. They showed no significant difference compared with those of the traumatic brain injury patients (78.75 pg/mL and 96.00 pg/mL, respectively). Multivariate Cox regression analysis in cardiac arrest patients identified only the S-100B level measured 12 hrs after study entry as an independent predictor for unfavorable neurologic outcome according to the Glasgow Outcome Scale score. In contrast, S-100B as well as interleukin-8 levels quantified 12 hrs after admission significantly predicted an unfavorable neurologic course in the traumatic brain injury group. CONCLUSIONS: Significantly elevated S-100B and interleukin-8 serum levels 12 hrs after cardiac arrest suggest that primary brain damage and systemic inflammatory response are comparably serious with that of traumatic brain injury. In both collectives, increased S-100B values measured 12 hrs after insult correlated well with an unfavorable neurologic outcome after 12 months.

Assessment of early brain damage in carotid endarterectomy: evaluation of S-100B serum levels and somatosensory evoked potentials in a pilot study.

The release of the neuronal protein S-100B into the circulation has been suggested as an early indication of cellular brain damage. The objective of this prospective pilot study was to determine S-100B serum levels in patients undergoing cross-clamping during carotid endarterectomy (CEA) and to correlate the results with the monitoring of somatosensory evoked potentials (SSEP) and the neurological short-term outcome. Arterial blood samples of 21 patients were drawn before oral intubation, cross-clamping, and unclamping, as well as before extubation and 6 hours later. Recording of SSEP was obtained during carotid occlusion and reperfusion. If loss of SSEP appeared, cerebral ischemia was assumed and an intraluminal shunt was placed. During cross-clamping, S-100B serum levels of 14 patients increased significantly from 0.05 ng/ml to 0.21 ng/ml, but returned to baseline levels after unclamping. In 5 cases, loss of SSEP amplitudes occurred but was reversed by the shunt insertion. No significant differences of S-100B serum values, neurological examination, and carotid duplex surveillance became obvious in this group when compared to the patients with undisturbed SSEP. However, 2 patients with complete disappearance of postcentral SSEP components suffered from neurological deficits in the postoperative period. S-100B serum levels remained highly elevated 6 hours after extubation (0.78 ng/ml and 0.41 ng/ml) compared to the baseline values (0.15 ng/ml and 0.07 ng/ml). During CEA a transitory increase of the S-100B serum levels appears to present an impairment of the blood-brain barrier integrity without any neurological deficits. In contrast, persistently elevated S-100B serum levels seem to be associated with transient loss of SSEP and development of neurological deficits.

Circulating mediators and organ function in patients undergoing planned relaparotomy vs conventional surgical therapy in severe secondary peritonitis.

HYPOTHESIS: Planned relaparotomy (PRL) has been suggested to have detrimental effects on the systemic activation of inflammation mediators, thereby enhancing organ dysfunctions as assessed by clinical scores in secondary peritonitis. DESIGN: Prospective, nonrandomized control trial. SETTING: Intensive care units of an urban and a university teaching hospital. PATIENTS: Twenty-nine patients with secondary peritonitis. INTERVENTIONS: Of the 29 patients with comparable initial peritonitis conditions, 11 underwent PRL and 18 obtained primary abdominal closure. Blood samples were obtained preoperatively and at 2, 6, 8, 12, 18, 24, 30, 36, 42, and 48 hours after the primary operation, then every 12th hour until day 5 and once daily until day 8. MAIN OUTCOME MEASURES: Quantification of circulating inflammation parameters (coagulation, acute-phase proteins, cytokine system, cell adhesion, opsonization) in correlation with Acute Physiology and Chronic Health Evaluation II, multiple organ failure, and Sepsis-Related Organ Failure Assessment scores. RESULTS: Preoperatively, the patient groups did not differ in mean age, cause of peritonitis, or clinical scores. On average, 5.1 (SEM, +/- 0.7; range, 3-11) lavage treatments were performed in the PRL group, with 90% of the procedures executed during the first 6 days. The PRL treatment resulted in a significantly higher need of blood components and an increased inflammation mediator response, especially concerning coagulation factors, proinflammatory cytokines, adhesion molecules, and opsonic parameters. During PRL, clinical score systems showed higher values and a delayed decline compared with primary abdominal closure treatment. Incidence of multiorgan failure, mortality, and the mean intensive care unit hospitalization period were clearly more pronounced in the PRL group. CONCLUSION: In our pilot study, additional lavage treatment of secondary peritonitis resulted in an enhancement of systemic inflammatory mediator response (in particular interleukin 8), which may contribute to a further impairment of organ function.

Chronic left heart catheterization for microvascular blood flow determination in the rabbit: a minimally invasive technique using specially designed port devices.

BACKGROUND: This study describes a modified catheterization technique with subcutaneously implanted port catheters to be inserted in a retrograde manner across the aortic valve into the left heart ventricle through the right carotid artery to measure organ perfusion. MATERIALS AND METHODS: The specially designed arterial port catheters were implanted in New Zealand rabbits (n = 11, 3.7 +/- 0.1 kg [mean +/- SEM]) under iv anesthesia (medetomidine/ketamine) and single-shot perioperative antibiotic therapy. Hemodynamics were registered continuously during the operation via an ear artery catheter. RESULTS: Implantation of ports was performed in all animals (11/11) without major complications (mean operation time: 70 +/- 3 min). We did not observe catheter-associated arrhythmia, fall in mean arterial pressure (MAP before and post OP: 70 +/- 2 and 68 +/- 2 Torr, respectively), or change in arterial oxygen saturation (SaO2 before and post OP: 89 +/- 3 and 95 +/- 2%, respectively). With a specifically modified microsurgical insertion technique, cerebral blood supply was effectively preserved as evidenced from postmortem histological examinations, cerebral blood flow determination with fluorescent microspheres, and measurement of S-100b protein serum concentrations, a specific marker of neuronal damage. The positioning of the catheter tip in the left ventricle was found to be correct in 10/11 animals. CONCLUSIONS: Repeated and atraumatic microsphere injections into the left ventricle have become feasible by transcutaneous puncture of subcutaneous port systems over several weeks under light sedation. Hence, this new approach (i) avoids the necessity of repeated intracardiac injections and port insertions via thoracotomy, thus reducing the perioperative stress for the animals, and (ii) allows for the first time minimally invasive repetitive and chronic measurements of regional organ blood flow under various experimental settings.