Sepsis score and acute-phase protein response as predictors of outcome in septic surgical patients

In a series of 135 patients with severe surgical infections, we determined the sepsis score and the plasma level of the acute-phase proteins alpha-1-acid glycoprotein, alpha 1-antitrypsin, complement factor B, and C3. The initial sepsis score was a strong determinant of survival: in survivors it was significantly lower than in nonsurvivors. Only 8% of patients with a sepsis score above 20 survived. At the onset of severe sepsis, the plasma levels of all four acute-phase proteins were significantly lower in nonsurvivors. A significant elevation of C3a levels in the plasma of both surviving and nonsurviving patients indicated marked consumption of complement components in all patients with severe sepsis. A linear equation was developed to predict survival: sepsis index of survival (SIS) % = 121 + 0.26 (complement factor B) + 0.36 (alpha-1-acid glycoprotein)-6 (sepsis score). Based on our analysis, at the onset of severe sepsis, an SIS of 50% or more can correctly predict 88% of survivors and an SIS less than 50% can correctly predict 86% of nonsurvivors several days in advance of clinical outcome.     

免疫因素在瘢痕疙瘩发生发展中的作用研究

目的探索免疫因素在瘢痕疙瘩发生中的作用。方法应用单向免疫扩散法和ＥＬＩＳＡ法等检测了７０例瘢痕疙瘩患者和５０例健康人的血清免疫球蛋白、补体和补体活化成分的浓度变化。结果与对照组相比，瘢痕疙瘩患者血清ＩｇＧ、ＩｇＡ、ＩｇＭ、ＩｇＤ、Ｃ３、Ｃ４、ＣＨ５０浓度显著降低，Ｃ３ｄ、ＳＣ５ｂ－９显著升高，有显著性差异（Ｐ＜０．０１）。且在瘢痕疙瘩患者中，进展期血清ＩｇＭ、ＩｇＡ、Ｃ４、ＣＨ５０浓度显著低于稳定期（Ｐ＜０．０１），Ｃ３ｄ、ＳＣ５ｂ－９则显著升高（Ｐ＜０．０１）。结论免疫因素可能在瘢痕疙瘩发病机理中具有重要作用，且对瘢痕疙瘩的发展有较大影响。     

Serum prognostic indicators in experimental Bacteroides peritonitis.

Serum lysozyme and hemolytic complement (CH100) levels were measured in dogs with experimental Bacteroides peritonitis. The CH100 levels showed little change in surviving animals. Nonsurvivors showed a moderate decrease in complement levels shortly after contamination. Both surviving and nonsurviving animals showed a slight initial decrease in lysozyme levels shortly after contamination. In surviving dogs this was followed by an increase to normal levels. In nonsurvivors, levels continued to increase, reaching a threefold magnification just prior to death. As a result of antibiotic therapy, CH100 levels exhibited no major changes; however, dogs deprived of antibiotic showed noticeable and persistent increases in lysozyme levels while treated animals showed only a mild elevation in lysozyme levels. The changes in the level of serum lysozyme may be a good indicator of antibiotic efficacy and approaching death from Bacteroides peritonitis.     

康肾片对老年维持性血透患者细胞免疫与体液免疫及补体系统的影响

目的 :探讨康肾片调节老年维持性血透患者免疫功能的作用机理。方法 :将老年肾衰竭患者 4 7例分为治疗组 35例、对照组 12例 ,均予常规血液透析。治疗组在透析的同时予口服康肾片。观察各组治疗前后CD3 + 、CD4+ 、CD8+ 、CD4+ /CD8+ ,IL - 1、IL - 2、IL - 6 ,IgG、IgA、IgM ,C3 、C4、CH50 水平的变化。结果 :治疗组治疗后 6个月CD3 + 、CD4+ 、CD4+ /CD8+ ,IL - 2 ,C3 、C4、CH50 明显上升 ;同时CD8+ 、IL - 1、IL - 6明显下降 ;IgG、IgA、IgM与治疗前相比则无明显变化 (P >0 .0 5 )。对照组治疗前后对比无显著性差异。结论 :康肾片可明显提高老年维持性血透患者CD3 + 、CD4+ 、CD4+ /CD8+ ,IL - 2 ,C3 、C4、CH50 异常降低的水平 ;可下调异常增高的CD8+ 、IL - 1、IL - 6的水平 ,具有调节老年维持性血透患者免疫失调的作用     

Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease.

Complement activation is necessary for an adequate immune and inflammatory response to infections. Activation releases anaphylatoxins that cause vasodilation, increase vascular permeability, and trigger release of polymorphonuclear neutrophil leukocyte (PMN) lysosomal enzyme and oxygen radicals. Under normal circumstances, an orderly progression of such events has a beneficial antimicrobial effect. The same mechanism, however, when uncontrolled, may damage host tissues. To provide information about the clinical importance of such events in sepsis, different complement parameters (C3, C4, and the desarginated forms of C3a [C3a(des)-Arg] and C5a [C5a(des)-Arg]), PMN elastase, and malondialdehyde (a by-product of membrane peroxidation by oxygen radicals) were measured daily in 26 septic patients and correlated with two objectively assessed and previously validated severity scores (acute physiology and chronic health evaluation [APACHE II] and Sepsis Severity Score [SSS]). Nonsurvivors (n = 12) had significantly greater and longer lasting complement activation than that in survivors, as reflected by higher levels of catabolic peptides (C3a(des)-Arg) and lower levels of native proteins (C3 and C4). C3a(des)-Arg, C3, C4, and the C3a(des)-Arg-C3 ratio were correlated with Sepsis Severity Scores. Polymorphonuclear neutrophil leukocyte elastase levels were higher in nonsurvivors and were correlated with C3a(des)-Arg and the C3a(des)-Arg-C3 ratio. Malondialdehyde levels were significantly higher in all patients than in controls, without, however, any relationship to severity of disease or clinical outcome. Since the higher and more persistent the complement activation and polymorphonuclear neutrophil leukocyte stimulation, the worse the patient's prognosis, we conclude that these mechanisms may be important in the clinical development of sepsis.     

Host defense against opportunist microorganisms following trauma. II. Changes in complement and immunoglobulins in patients with abdominal trauma and in septic patients without trauma

Total hemolytic complement (CH50), conversion of C3 by inulin and cobra venom factor (CoVF), and immunochemical levels of Clq, C4, C2, C3, C5, factor B, properdin, C3b inactivator (KAF), and immunoglobulins (Igs) G, A, and M were measured in the sera of ten patients with abdominal trauma and ten medical patients with septicemia without trauma. Reduction in C3 conversion by CoVF and decrease in the levels of properdin and KAF were demonstrated in the trauma sera. CH50 and the level of C5 were also decreased. Conversion of C3 by inulin and levels of factor B, Clq, C4, C2, and C3 were found to be normal in the patients' sera. Complement levels and activities were found to be normal in the sera of the septic non-trauma patients. A decrease in serum IgM was observed in both patient groups; levels of IgG and IgA were normal. These results indicated that abnormalities of immunoglobulin and of the alternative and classical complement pathways were associated with nonburn trauma. Moreover, the data suggested that consumption of the classical complement pathway associated with septicemia in the thermally injured patient resulted from synergism between the trauma and infection rather than from septicemia per se.     

Is hypocomplementemia useful for diagnosing or predicting extra-articular manifestations in patients with rheumatoid arthritis?

OBJECTIVE: Serum CH50 and C4 levels are usually normal or elevated in rheumatoid arthritis (RA) but are classically decreased in patients with serious extra-articular manifestations (SEAMs) of the disease. The objective of this study was to evaluate whether complement assays are useful in diagnosing or predicting SEAMs of RA. METHODS: First, a cross-sectional study of 405 patients admitted for RA compared patients with and without hypocomplementemia. Then, a retrospective longitudinal design was used to investigate within-patient complement level variations overtime. RESULTS: In the univariate analysis, patients with low CH50 and C4 levels were more likely to have vasculitis and/or cryoglobulinemia than those with normal CH50 and C4 levels, and nodules were more common in the patients with low than with normal C4 levels. In a multivariate model based on symptoms, low C4 was associated with vasculitis and pleurisy and low CH50 with vasculitis. However, these associations were too weak to make CH50 and C4 determination useful for detecting SEAMs, and the within-subject variations in patients with SEAMs limited the predictive value of these assays. CONCLUSION: Hypocomplementemia is of limited usefulness for detecting or predicting SEAMs.     

The effects of aortic reconstruction and collagen impregnation of Dacron prostheses on the complement system.

Complement activation has been associated with numerous clinical hazards such as platelet aggregation, adult respiratory distress syndrome, and renal dysfunction. The complement system is activated by exposure of different biomaterials to blood. Recently a watertight knitted Dacron aortic prosthesis impregnated with bovine collagen has been developed. One potential disadvantage is that this bovine collagen may activate the complement system and evoke the production of inflammatory mediators. We conducted a prospective randomized trial to study the systemic effects of collagen-impregnated prostheses and of aortic surgery with implantation of Dacron prosthesis on the complement system in the perioperative period and at 3 months after operation. Forty-one patients randomly received either a collagen-impregnated (n = 20) or a nonimpregnated prosthesis (n = 21). Twelve patients who had cholecystectomy served as controls. CH50 consumption and C3a generation were determined to study overall complement activation. Furthermore, C3a/C3 fractions were calculated. Finally, C4 and factor B consumption were determined to evaluate the complement stimulation via the classic and the alternative pathways, respectively. We found significant activation of the complement system during the operation in both the collagen group (CH50 consumption: 40%, p = 0.03; C4 consumption: 74%, p < 0.0001; factor B consumption: 73%, p < 0.0001; C3a/C3 fraction increase: 173%,p = 0.04), and the nonimpregnated group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 71%, p < 0.0001; factor B consumption: 76%, p < 0.0001; C3a/C3 fraction increase: 165%, p = 0.025), with no statistically significant differences between the groups of prostheses. Activation was initiated via both the classic and the alternative pathway. This indicates aortic implantation significantly activates the complement system, but that collagen-impregnated prostheses do not stimulate the complement system any more than its nonsealed substrate. Comparing results in patients with vascular disease with controls, a significantly increased complement activation was observed in the vascular group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 74%, p < 0.0001; factor B consumption: 75%, p < 0.0001; C3a/C3 fraction: 169%, p = 0.002), compared with the controls (CH50 consumption: 71%; C4 consumption: 104%; factor B consumption: 94%; C3a/C3 fraction: 119%, all p = NS), with statistical significant differences between the vascular group and cholecystectomies (CH50: p = 0.005; C4: p = 0.002; factor B: p < 0.0001, and C3a/C3 fraction: NS). This observation demonstrates that aortic surgery with the implantation of a Dacron prosthesis significantly activates the complement system.     

Inclusion of sevoflurane in cardioplegia reduces neutrophil activity during cardiopulmonary bypass

OBJECTIVE: The purpose of this study was to examine the effects of sevoflurane cardioplegia on neutrophil response and complement activation after cardiopulmonary bypass (CPB). DESIGN: A prospective, randomized clinical investigation. SETTING: University-affiliated hospital; single institutional. PARTICIPANTS: Twenty-one male patients undergoing coronary bypass surgery using CPB. INTERVENTIONS: Eleven patients were randomly assigned to receive sevoflurane 2% as a part of the cardioplegic mixture (SEV). The control group (n = 10) received no sevoflurane in their cardioplegia (control). MEASUREMENTS AND MAIN RESULTS: Myeloperoxidase activity (MPO) was assayed in coronary sinus blood as a surrogate for neutrophilic response at the termination of CPB. MPO activity in the coronary sinus blood was lower in the patients who received sevoflurane compared with controls. MPO activity was higher in patients with cardiac events at 4-year follow-up when compared with asymptomatic patients. IL-8, C4b, C3d, C5a, and CH50 were assessed in coronary sinus and peripheral blood at time of CPB initiation (T0) and upon the termination of CPB (T2). Peripheral blood sampling occurred at the sixth hour after T0 (T6). IL-8 levels were significantly inhibited in the SEV group when compared with controls at T2 and T6. CH50 (an index of global activation of complement system) decreased 30% at T2 and 52% at T6. The classic component of the complement pathway (C4b) was effectively inhibited in the SEV group, whereas the common pathway (C3d and C5a) was similar in both groups. CONCLUSIONS: The addition of sevoflurane to cardioplegia is associated with an inhibition of neutrophils after CPB. A major component of the neutrophil response appears to be IL-8 mediated, although the classic complement pathway is also inhibited by sevoflurane.     

Impact of in vivo complement activation and cryoglobulins on graft outcome of HCV-infected renal allograft recipients

BACKGROUND: Chronic hepatitis C virus (HCV) infection is closely associated with mixed cryoglobulinemia. Cryoglobulins can activate complement leading to vascular damage. We examined whether cryoglobulinemia and complement turnover is associated with HCV infection in renal transplant recipients and whether this has an adverse effect on graft outcome. METHODS: Sera and fresh plasma from 31 HCV-RNA-positive patients after renal transplantation (group I) were studied for cryoglobulins, complement hemolytic activity (CH50), and complement split product C3d. In total, 80 HCV-negative renal transplant recipients (group II) and 72 untreated patients with chronic hepatitis C (group III) without renal transplantation served as controls. RESULTS: Cryoglobulins were detected in 45, 28, and 26% of the patients in group I, II, and III, respectively. A high cryocrit ( > 5%) was present only in patients of group III (p < 0.01%). Mean CH50 values were lower and C3d levels higher in HCV-positive patients (group I and III) compared with HCV-negative patients (p < 0.0001). Cryoglobulins were not associated with extrahepatic manifestations or graft dysfunction, except in five patients of group III demonstrating cryoglobulinemic vasculitis. HCV-positive renal transplant recipients with signs of complement activation showed a significantly greater increase of serum creatinine (0.88 +/- 1.14 mg/dL) when compared with baseline than patients without complement activation (0.34 +/- 0.37 mg/dL; p = 0.035). There was also a tendency toward a higher extent of proteinuria in patients with complement activation (1.38 +/- 2.17 g/d vs. 0.50 +/- 0.77 g/d; p = 0.25, NS). CONCLUSIONS: Cryoglobulins are common in renal allograft recipients, but do not affect graft function. However, complement activation appears to be involved in chronic allograft dysfunction in HCV-infected recipients.     

Die zirkulierenden Adhäsionsmoleküle sICAM-1 und sE-Selectin bei Patienten mit Sepsis

Aim: The aim of this study was to investigate whether the plasma levels of the circulating adhesion molecules sICAM-1 and sE-selectin could serve as early predictors of developing sepsis and its severity. Methods: Twenty-four patients admitted to an intensive care unit with a high risk of developing septic complications were enrolled in this study. Patients were divided into three groups: group I, with infection without systemic sepsis, n = 8; group II, surviving patients with severe sepsis and multi-organ failure (MOF), n = 8; and group III, nonsurviving patients with severe sepsis and MOF, n = 8. Classification of patients was performed according to the clinical criteria defined by the Sepsis Consensus Conference in 1992. Blood samples were taken at 7 a.m. starting from the day of admission until the 7th day after diagnosis of sepsis. Plasma levels of sICAM-1 and sE-selectin were determined in all samples taken between the 3rd pre-septic day and the 7th day after the diagnosis of sepsis was made. Results: In group I, both sICAM-1 (354.21 ± 128.60 ng/ml, 86 samples) and sE-selectin (30.41 ± 7.20 ng/ml, 86 samples) levels remained within the reference range over the whole period of observation. The sICAM-1 levels of group II (between 550.82 ± 275.67 ng/ml and 445.08 ± 243.63 ng/ml) tended to show values above the reference range without being significant. Mean sICAM-1 levels in group II did not differ from those of group I. From the 2nd pre-septic day onwards the sICAM-1 levels of group III increased, but not significantly. Significant differences in sICAM-1 levels between group I and group III were observed, with peaks at the samples of the 2nd pre-septic day and after the 3rd day of sepsis, respectively (P < 0.05). The sE-selectin levels in group II were elevated from the 3rd pre-septic day onwards, with a peak value on the 2nd day of sepsis (P < 0.05). Afterwards, levels decreased to initial values despite ongoing sepsis. Mean values of sE-selectin levels of group I and II were significantly different with the onset of sepsis (P < 0.05). Plasma levels of sE-selectin in group III were significantly elevated (66.30 ± 9.00 ng/ml on the 3rd pre-septic day), reaching their maximal values of 106.67 ± 21.66 ng/ml at the end of the observation period. Significant differences between sE-selectin levels of groups I and III existed from the 3rd pre-septic day onwards, and between group II and III on the 7th and 8th day of sepsis. Conclusion: Our results show that sICAM-1 is a relatively non-specific indicator for sepsis. In contrast, sE-selectin seems to be a good and early predictor of the beginning of severe sepsis with MOF. Furthermore, sE-selectin levels seem to have a prognostic value for the severity, possible course, and outcome of developing sepsis.     

静脉预注H1,H2受体阻滞药对减轻鱼精蛋白副作用的研究

将３０例ＡＳＤ、ＶＳＤ患者随机分为对照与预防用药两组，对比观察Ｈ１、Ｈ２受体阻滞药苯海拉明、西米替丁对减轻鱼精蛋白副作用的效果和应用鱼精蛋白后补体Ｃ３、Ｃ４、ＣＨ５０浓度变化。结果发现预防用药组血液动力学变化明显小于对照组，两组之间差异显著（Ｐ＜０．０１）。应用鱼精蛋白后Ｃ３、Ｃ４、ＣＨ５０均下降，与用药前相比差异显著（Ｐ＜０．０１）。提示鱼精蛋白中和肝素可引起补体激活、组胺释放，Ｈ１、Ｈ２受体阻滞药能够减轻鱼精蛋白引起的血压下降。     

Tumor angiogenesis, apoptosis, and p53 oncogene in stage I lung adenocarcinoma

The purpose of this study was to clarify which factors are important as predictors not only of patient survival but also of hematogenic metastasis in 15 patients with stage I lung adenocarcinoma who underwent curative operation. The relationship between tumor angiogenesis, apoptosis, and p53 oncogene was also studied. A total of 15 patients were divided into two groups: surviving group (n=7) and nonsurviving (metastasis) group (n=8). We studied the medical charts, operative records, pathologic reports, and tumor specimens taken at surgical resection. We measured the apoptotic index using the ApopTag kit and the intratumoral microvessel count using an anti-CD34 monoclonal antibody. In addition, immunohistochemical staining for the expression of p53 was conducted simultaneously. The clinicopathological characteristics, including age, sex, tumor size (pT), and histological differentiation, were not significantly different between the surviving and the nonsurviving group. The microvessel count was significantly higher in nonsurviving group than in the surviving group. The apoptotic index and the expression of p53 was not significantly different between the two groups. An inverse correlation between the apoptotic index and microvessel count, and a positive correlation between the expression of p53 and microvessel count, were observed. Angiogenesis may be an important prognostic factor in patients with stage I lung adenocarcinoma.     

Activation of complement and serial changes of anaphylatoxin (C3a, C5a) in patients for open-heart surgery using a membrane oxygenator]

Activation of complement and serum changes in anaphylatoxin (C3a and C5a) were studied in 8 patients who underwent open-heart surgery using a membrane oxygenator. C1 esterase inhibitor (C1-EI), C3, C5, CH50, C3a and C5a were measured serially at 7 points. C1-EI, C3, and C5 were measured by single radial immunodiffusion, CH50 by Mayer's method, and C3a and C5a by radioimmunoassay. Levels of C1-EI, C3 and C5 decreased significantly from 10 min after initiation to 120 min after the end of CPB compared with base line values. Degree of activation of complement increased in proportion to duration of CPB. Significant decreases of C3 and C5 continued until first postoperative day. Level of C3a increased significantly 10 min after initiation of CPB, and gradually increased till immediately after the end of CPB, when the level was maximum (4625 +/- 560 ng.ml-1) among 7 points. Level of C3a decreased gradually till 120 min after end of CPB. C5a was not detected during whole course. No patient showed respiratory distress of pulmonary edema. In conclusion, membrane oxygenator activated classical pathway of complement at 10 min after initiation of CPB. C3a increased significantly from 10 min after initiation of CPB to 120 min after end of CPB, but C5a was not detected at all during the whole course. The significant activation of complement continued till first postoperative day.     

Complement and the severity of pulmonary failure

Complement-induced granulocyte aggregation is suspected as a cause of the adult respiratory distress syndrome. Quantifying the lung damage in these patients is difficult, and complement levels combined with clinical parameters of oxygenation might help define the severity of pulmonary deterioration. Forty-five high-risk patients, selected by arterial blood gas criteria, had their pulmonary insult related to C3a and C5a levels. Patients were stratified by pulmonary shunt, alveolar-arterial oxygen gradient, and radiographic findings into two categories of severity: pulmonary dysfunction, a milder insult, and ARDS, a major aberration in pulmonary function. The clinical assignment of a diagnostic category required at least 96 hours of monitoring. During this 96-hour period, multiple complement levels were obtained. These complement levels were then compared in pulmonary dysfunction and ARDS patients. ARDS patients had significantly higher C3a and C5a values after the patients were selected as high risk. These results suggest that the amount of complement activated in patients with incipient respiratory failure correlates with the severity of eventual pulmonary insult. The use of arterial blood gases and C3a and C5a levels should allow better and earlier definition of patients at risk for ARDS.     

Complement levels in septic primates treated with anti-C5a antibodies

During gram-negative sepsis it is known that endotoxin activates complement by the alternate pathway. The complement anaphylatoxin C5a, a result of this activation, is thought to play a key role in attracting and activating neutrophils in the lungs, leading to the adult respiratory distress syndrome. Complement levels were measured in primates made septic by Escherichia coli infusions. Anti-human C5a antibodies were administered to study their effect on neutrophil-mediated lung injury. Control (I), septic (II) and septic + anti-C5a antibody (III) groups (n = 4) were studied. The antibody-treated group (III) demonstrated a significant attenuation of septic shock and pulmonary edema as has been previously reported. All complement profiles were corrected for varying hemoglobin concentrations. C3, C4, and C5 levels were measured by radial immunodiffusion and were depleted in both septic groups. Once the levels were depleted from the plasma, they did not recover. The depletion of C4 indicates that classical pathway activation also occurred. C3a, C4a, and C5a levels were measured by radioimmunoassay. Significantly increased peak levels were reached in the septic groups 15 min after initiation of the E. coli infusion. There were no significant differences in early peak C3a and C4a levels between groups II and III. However, the mean peak C5a level in group III (anti-C5a antibodies) was 42% lower than that in group II, and after this early peak, C5a levels were not elevated above control levels in group III. The antibody to human C5a was thus shown to be cross-reactive with primate C5a and was specific since C3a and C4a levels were not decreased in group III.(ABSTRACT TRUNCATED AT 250 WORDS)     

甲状腺激素、降钙素原和C-反应蛋白对脓毒症患者病情及预后评估的价值

目的结合脓毒症患者病情、住院病死率探讨血清甲状腺激素（TH）、血清降钙素原（PCT）和C-反应蛋白（CRP）三者对脓毒症患者预后的评估价值。 方法采用回顾性研究,根据2008年国际脓毒症定义的脓毒症诊断标准,将入选病例分为脓毒症组、严重脓毒症组（包括严重脓毒症及脓毒症休克患者）、非全身炎症反应综合征（SIRS）对照组;脓毒症、严重脓毒症组按照患者的住院病死率,分为存活组及死亡组。测定各组患者入院24 h内的TH、PCT及CRP浓度并进行各组间的统计学分析。 结果严重脓毒症患者血清FT₃、TT₃、TT₄水平显著低于脓毒症及对照组（P均< 0.05）,脓毒症患者血清FT₃、TT₃水平低于对照组（P均< 0.05）;脓毒症及严重脓毒症患者血清PCT、CRP水平显著高于对照组（P均< 0.05）,严重脓毒症患者较脓毒症患者血清PCT水平显著升高（P < 0.05）,但两组CRP水平差异无统计学意义;死亡组FT₃、TT₃、PCT水平显著高于存活组（P均< 0.05）,但CRP差异无统计学意义;各组的TSH含量变化无统计学意义。 结论CRP是鉴别SIRS和非SIRS的有效指标,但并非早期诊断脓毒症的可靠指标。PCT、TH是早期诊断脓毒症并能与非SIRS鉴别的特异性较高的炎症指标;结合PCT和TH水平可以客观判断脓毒症病情的严重性。同时,TH与PCT水平与脓毒症预后显著相关,两者联合应用有望成为早期判断脓毒症预后的快速、可靠且非有创性指标。     

Effects on C3 and CH50 levels during and following extracorporeal whole body hyperthermia

Cardiopulmonary bypass can affect inflammatory reactions and evoke the "postperfusion syndrome," manifested as multiple organ dysfunction in the recovery period. This syndrome is generated by the activation of complement, macrophages, neutrophils, and inflammatory cytokines. Following the use of hypothermia during cardiac procedures, active hyperthermic rewarming is used to reestablish body temperature. Complement levels and their interactions have been investigated during and following hypothermia. Hyperthermia is being used clinically; however, the effect of markedly elevated temperatures on complement is unknown and, therefore, needs to be investigated. A pilot canine study was designed to begin to explore what role hyperthermia may play on complement levels during and following extracorporeal whole body hyperthermia. Five dogs were heated to a core temperature of approximately 42 degrees C, held at this elevated temperature for 90 minutes, then cooled to normothermia. A decline in C3 levels at the end of warming with further declines through day 4 post treatment was observed. CH50 levels mimicked the C3 level decline; however, there was a trend for rebounding by day 4. The findings involving complement factors following hyperthermia signify that this increase in temperature causes a decrease in both C3 and CH50 levels.     

Ionized calcium, parathormone, and mortality in critically ill surgical patients.

A prospective study measured ionized calcium and parathormone sequentially at 48- to 72-hour intervals in 25 surgical intensive care unit patients. Twelve patients (48%) died at mean day 40 and median day 26. Levels of ionized calcium, parathormone, blood urea nitrogen, creatinine, albumin, magnesium, and phosphate for patients who lived were compared with levels for patients who died. The incidence of hypotension, renal failure (creatinine greater than or equal to 3.0), and bacteremia, as well as the amount of red cell, crystalloid, and colloid administration for the two groups was compared. Hypotension, bacteremia, red cells, crystalloid, and colloid were no different. On days 1 and 2 ionized calcium levels were significantly lower and parathormone levels significantly higher in nonsurviving patients; this difference persisted through days 3 and 4. Blood urea nitrogen and creatinine levels increased early in nonsurviving patients but renal failure, which occurred in nine nonsurviving patients, did not develop until mean day 14, median day 18. The phosphate level was slightly higher but still within normal range in nonsurviving patients. By days 5 and 6 ionized calcium and parathormone levels were no different in nonsurviving patients, despite there being no improvement in renal function. Magnesium and albumin levels were no different between groups. Ionized calcium levels are lower and parathormone levels higher early in nonsurviving patients. This difference is not readily explained by associated clinical conditions, including renal dysfunction. Although etiology remains unclear, low ionized calcium and elevated parathormone are early predictors of mortality in critically ill surgical patients.     

Anaphylatoxin generation in multisystem organ failure

Complement components were studied in 44 patients with extensive injuries or infections. The concentrations of anaphylatoxins (C4a, C3a, and C5a) and other complement components (C1INH, C4, C3, and C5) were determined in plasma using radioimmunoassay and rocket immunoelectrophoresis techniques. The results were correlated with the development of multisystem organ failure (MSOF). In particular, plasma concentrations of C3a and C4a were found elevated in trauma patients. These elevated anaphylatoxin levels were correlated with severity of the injury. As reported in other types of patients, the apparent C5a plasma levels were not elevated. Therapy reduced the plasma levels of C3a with great predictability. It appears that plasma C3a and C4a levels may relate not only to severity of the injury but may signal onset of secondary events such as bacteremia. Consequently, longitudinal monitoring of anaphylatoxin levels may prove helpful in diagnosing the status of trauma patients.