Alterations of cell-mediated immunity following cardiac operations: clinical implications and open questions.

Cardiac surgery with cardiopulmonary bypass (CPB) is known to induce an immune response whose nature has been increasingly elucidated during the recent decade. Clinically, patients usually show two to three of the four symptoms, which define the so-called systemic inflammatory response syndrome (SIRS). In addition, all parameters of the innate, nonspecific immune system, e.g., polymorphonuclear cells, elastase, and complement, are activated. This also applies to the proinflammatory mediators interleukin (IL)-1beta, -6, and -8, and tumor necrosis factor (TNF)-alpha. Within the adaptive, specific immune system, a decrease of T lymphocytes and T helper (TH) cells is observed, whereas suppressor/ cytotoxic T cells and B cells appear to be nearly unaffected. Cytokine measurements provide more detailed information: IL-2 and IL-12, which are important for the activation of the type-1 TH-cell (TH1)-mediated immune response, are depressed following cardiac operation. In contrast, IL-10 and transforming growth factor-beta essential to TH2-mediated humoral or anti-inflammatory immune response, are upregulated. In vivo tests, e.g., delayed type hypersensitivity skin reaction and tetanus antibody production, confirm the polarization of the adaptive immune response towards the TH2 pathway. However, all these alterations usually do not result in clinical adverse events. Therefore, more information is needed about the immune response of patients at high preoperative risk or with serious perioperative complications to find out whether clinically relevant events are correlated to alterations of immune response. For this purpose, more readily available, standardized methods for immunologic monitoring appear highly desirable.

Detection of acute phase response and infection. The role of procalcitonin and C-reactive protein.

OBJECTIVE: Established parameters, e.g. C-reactive protein (CRP), do not differentiate specifically enough between patients developing an infection and those exhibiting an acute phase response following cardiac surgery. The objective of this prospective study was to investigate if procalcitonin (PCT) is more helpful than CRP. METHODS: During a 1-year period, seven out of 563 patients (1.2%) developed systemic infections (group A) after cardiac operations with cardiopulmonary bypass (CPB), and additional eight patients (1.4%) had local wound infections requiring surgical therapy (group B). Blood samples for PCT and CRP measurements were taken preoperatively, at the onset of infection (d1), as well as on the third day (d3), fifth day (d5), and seventh day (d7) following diagnosis of infection. Forty-four randomly selected patients undergoing cardiac surgery with CPB without clinical signs of infection, additional intensive care unit (ICU) management or additional antibiotic treatment served as control (group C) to assess the PCT and CRP contribution to acute phase response. PCT and CRP levels were measured preoperatively, on the first (d1), third (d3) and fifth day (d5) after operation. RESULTS: At the onset of infection, PCT levels (median interquartile range 25%-75%) increased significantly in group A as compared to baseline values (10.86 (3.28-15.13) ng/ml vs. 0.12 (0.08-0.21) ng/ml), and decreased during treatment to still significantly elevated values on d5 (0.56 (0.51-0.85) ng/ml). CRP levels were significantly elevated on all days investigated with no trend towards normalisation (d1: 164.5 (137-223) mg/l) vs. 1.95 (1.1-2.8) mg/l preoperatively, d5: 181.1 (134-189.6) mg/l. In group B, no increase in PCT levels, but a significant increase of CRP from d1 (165.9 (96.6-181.6) mg/l) vs. 3.7 (2-4.3) mg/l preoperatively) until d5 98 (92.8-226.2) mg/l was detected. In group C, postoperative PCT levels increased slightly but significantly in the absence of infection on d1 (0.46 (0.26-0.77) ng/ml vs. 0.13 (0.08-0.19) ng/ml preoperatively), and d3 (0.37 (0.2-0.65) ng/ml and reached baseline on d5 (0.24 (0.11-0.51) ng/ml)). CRP levels were significantly elevated as compared to baseline on all postoperative days investigated (baseline: 1.75 (0.6-2.9) mg/l, d1: 97.5 (74.5-120) mg/l), d3: 114 (83.05-168.5) mg/l, d5: 51.4 (27.4-99.8) mg/l)). PCT showed a significant correlation to CRP in group A (r =0.48, p < 0.001), a weak correlation in group C (r=0.27, p=0.002) and no correlation in group B. Intergroup comparison revealed a significant difference for PCT between all groups (A>C>B) and significantly higher CRP levels in group A vs. C and in group B vs. C. Thus, the pattern high PCT/high CRP appears to indicate a systemic infection, while low PCT/high CRP indicates either acute phase response or local wound problems, but no systemic infection. The cost for PCT measurements was 5.6-fold higher as compared to CRP. CONCLUSION: Due to the significant differences in the degree of increase, PCT appears to be useful in discriminating between acute phase response following cardiac surgery with CPB or local problems and systemic infections, with additional CRP-measurement increasing the specificity.

Early extubation after cardiac surgery: a prospective clinical trial including patients at risk.

BACKGROUND: Recent evidence suggests that early extubation after cardiac surgery can be performed without increased morbidity, resulting in economic advantages. However, most studies on this subject exclude patients with preoperative risk factors described as predictors for prolonged mechanical ventilation. The purpose of our prospective clinical trial was to decide whether early extubation is feasible independent of preoperative patient status, in particular independent of preoperative risk factors. METHODS: From 12/96 to 6/97, 266 patients underwent cardiac surgery, most commonly CABG and valve replacement. 65 patients (24.4%) formed the risk group, showing preoperatively at least one of the following risk factors: emergency surgery, severe left-ventricular dysfunction, previous heart surgery, recent myocardial infarction, age 75 years or older, history of several myocardial infarctions. The remaining 201 patients (75.6%) formed the control group. The percentage of patients extubated within 12 hours represented the primary endpoint. 38 patients (10 risk, 28 control) had to be excluded from further analyses due to intra- or perioperative complications. RESULTS: No differences between 55 risk patients and 173 control patients could be detected in extubation rate within 12 hours (100% vs 100%), mean extubation time (6:04 h vs 6:01 h), and incidence of complications after extubation (5.5% vs 5.2%). Risk patients were discharged 0.33 days later from the intensive care unit (2.00 d vs 1.67 d; p = 0.047). CONCLUSIONS: 1. All patients are basically suitable for early extubation, with the presence of preoperative risk factors used in this study being poor predictors of prolonged ventilation. 2. The necessity of prolonged ventilation is primarily determined by intra- or perioperative complications.

In vitro studies on PMN-independent endothelial cell damage in trauma: decrease of PMN-endothelial cell adherence by fibrinogen degradation products and disturbance of endothelial cell membrane integrity by trauma serum.

Trauma favors the development of adult respiratory distress syndrome (ARDS). Adherence of polymorphonuclear leukocytes (PMN) to endothelial cells (EC) with subsequent EC damage by the respiratory burst products and proteases of the PMN is thought to be one of the basic mechanisms in the pathogenesis of ARDS. Recent studies have shown that there might also be PMN-independent mechanisms of EC damage. It would speak for PMN-independent EC damage if in the state of risk for this damage factors were found which decrease PMN activity or if EC damage appeared without PMN. Because in trauma and sepsis pathologic coagulation with high levels of fibrinogen degradation products (FDP) is often diagnosed, we investigated whether FDP-D and FDP-E might influence PMN adherence to EC. We also investigated whether serum of traumatized patients might provoke EC damage in a PMN-independent system in vitro. To achieve this we evaluated the viability of EC using a fluorescence staining method. We found that both FDP-D and FDP-E decreased PMN adherence to human EC significantly (p < 0.01) at a concentration of 50 micrograms/ml. Furthermore we found that EC membrane integrity can be disturbed by serum of trauma patients. These results suggest that in trauma also PMN-independent mechanisms are important for EC damage.

Tc-99m HMPAO cerebral scintigraphy. A reliable, noninvasive method for determination of brain death.

To determine the usefulness of cerebral blood flow imaging for the diagnosis of brain death, 4 female and 12 male patients, aged 19 to 69 years and suffering from various intracranial lesions, were studied. In addition to neurologic examination, electroencephalographic recording, and cerebral angiography, tomographic brain scintigraphy was performed using a SPECT system with a LEAP collimator after the intravenous administration of 555 MBq Tc-99m HMPAO. The radioisotopic scanning procedure revealed no intracranial perfusion in 14 of the 16 patients. Only minimal cerebellar blood flow was seen in one patient. In another, residual right-sided supratentorial flow was initially present but absent in a follow-up HMPAO SPECT. Carotid angiography (four-vessel contrast media angiography) confirmed the above results without exception. Because HMPAO is taken up by normal brain tissue with no significant redistribution for several hours, the tracer is particularly helpful in cases of suspected brain death. The quality of the tracer must be established by chromatography. Interpretation of the SPECT images produces reliable and reproducible results. In conclusion, cerebral blood flow imaging with HMPAO is a safe, noninvasive procedure for the determination of brain death, that produces fast, reliable, reproducible, and easy-to-interpret results.

[Early management of the intrathoracic area]. / Frühversorgung im Intrathorakalbereich.

The procedures of preclinical management of chest injuries are presented. Emphasis is put on the different aspects of "acute thorax": sucking chest wound, pericardial tamponade, oligemic shock and open thorax. The primary acute management includes the chest tube, intubation, ventilation, pericardiocentesis and surgical management of penetrating chest trauma. The different in the literature are discussed.

[Poly-, multiple trauma and intra-abdominal injuries]. / Poly-, Multitrauma und intraabdominelle Verletzungen.

The present work deals with the problem of abdominal injuries in polytraumatized patients. The results were obtained from a retrospective study of the records of 530 polytraumatized patients treated at the Central Hospital of the German Federal Armed Forces (Bundeswehr). In all, 193 of these patients had abdominal injuries. The overall mortality was 23.8% (n = 126): mortality among the patients with abdominal injuries was 26% (n = 50). Abdominal injuries alone led to death in 9.1% (n = 1), but mortality increased to 18.4% when at least one extra-abdominal injuries was also present. A combination of abdominal injuries and two or more extra-abdominal lesion led to a mortality rate of 27%. Mortality was found to be age- and sex-related: in young children and patients over 55 years (especially those around 70) mortality was 33.3%-72%. Among the cases with fatal outcome there was a female-to-male ratio of 3:2. The most common causes of death were: hemorrhage shock (62.3%), head injuries (37.7%), septicemia (8.1%), pneumonia, and ARDS (5.4% each). Within the last eight years we have used the following supplementary examination methods: computed tomography, peritoneal lavage, and ultrasonography. The retrospective study has shown that CT is not the examination of choice. The reliability with lavage and ultrasonography was approximately the same, but lavage was found to be more dangerous. Therefore, we abandoned lavage and used sonography only. However, we are of the opinion that any surgeon should use the examination method that has yielded the best results for him or her, to ensure the best possible outcome for the patient.