Cytokine induction by LVAD in the canine kidney.

BACKGROUND: The outcome of left ventricular assist device (LVAD) support is reported to be associated with proinflammatory cytokines. We investigated the effect of LVAD support on renal function and the resultant cytokine induction. METHODS: A prospective experimental study was performed using 15 mongrel dogs weighing 14 to 36 kg. LVAD was introduced in nine dogs (LVAD group) and the remaining six dogs were managed without LVAD support (control group). All animals were observed for six hours after thoracotomy. Renal regional blood flow was measured, and albumin-creatinine ratio (ACR) and N-acetyl-beta-D-glucoseaminidase index (NAGI) were evaluated as parameters of glomerular and tubular function, respectively. Tumor necrosis factor alpha (TNF-alpha) concentrations in the blood and homogenate of renal tissues were measured and immunohistological examination of renal tissues was conducted by means of anti-nuclear factor kappa B (NF-kappa B), TNF-alpha and interleukin 1 beta (IL- 1 beta) antibodies. RESULTS: In the LVAD group, the renal cortex-medullar blood flow ratio significantly (p<0.05) decreased, and ACR was significantly (p<0.05) higher than in the control group, indicating glomerular insufficiency. There were no significant differences in NAGI and TNF-alpha levels in the blood and renal tissues between the two groups. Immunohistological examination of renal tissues demonstrated an accumulation of NF-kappa B, TNF-alpha, and IL-1 beta in the LVAD group. CONCLUSIONS: An LVAD alters renal regional blood flow and induces a small amount of cytokines. We speculate that if an LVAD is introduced during systemic inflammatory response syndrome, the LVAD will induce a second attack resulting in multiorgan failure. For successful LVAD support, the appropriate selection of time periods is essential.     

腹腔镜和开腹胆囊切除术对患者血清细胞因子IL-6、IL-10和IL-18的影响

目的:探讨腹腔镜胆囊切除术(LC)和开腹胆囊切除术(OC)对慢性结石性胆囊炎患者血清IL-6、IL-10和IL-18影响,比较两种方法对机体肝功能的损伤和机制。方法:选择LC患者和OC患者各30例,分别于术前、术后1d、5d抽取静脉血测定血清ALT、AST、IL-6、IL-10和IL-18含量,并进行对比研究。结果:LC组和OC组术后血清ALT、AST、IL-6和IL-18含量均较术前增加(P<0.01),血清IL-10含量较术前降低(P<0.01),上述指标术后1d变化最为明显,LC组上述血清指标变化小于同期OC组(P<0.05)。结论:LC对患者肝功能损伤较OC小,可能与LC刺激机体产生IL-6和IL-18较少,维持较高血清IL-10水平,维护适度机体细胞因子平衡有关。     

The analysis of the usefulness of laparoscopic microwave coagulation therapy for hepatocellular carcinoma in patients with poor hepatic reserve by serial measurements of IL-6, cytokine antagonists,and C-reactive protein

Background: Little is known about the effectiveness of laparoscopic microwave coagulation therapy (L-MCT) for hepatocellular carcinoma (HCC) in patients with liver cirrhosis and poor hepatic reserve. Here, we analyzed the usefulness of laparoscopic MCT by comparing the serum levels of IL-6, cytokine antagonists, and C-reactive protein (CRP) following L-MCT with those following MCT with the open method (O-MCT). Methods: Sixteen patients with hepatocellular carcinoma (HCC) were separated into L-MCT and O-MCT groups according to ICGR15 (ICGR15 30%<:L-MCT, 30%> :O-MCT). Nine patients with poorer hepatic reserve received L-MCT, while seven patients with relatively good hepatic reserve received O-MCT. Serum levels of cytokine antagonists (interleukin-6, IL-6; interleukin-1 receptor antagonist, IL-1ra; soluble tumor necrosis factor receptor type I, sTNF-R55) and C-reactive protein (CRP) were simultaneously measured on serial postoperative days (POD) by immunoassay. Results: Postoperative serum levels of IL-6, IL-1ra, and CRP were significantly elevated on POD-1 and returned to the preoperative levels on POD-7 in both L-MCT and O-MCT groups. In contrast, no significant elevation of sTNF-R55 was found during the period in both groups. In addition, no statistical differences were found in the levels of IL-6, IL-1ra, sTNF-R, and CRP between the groups, except that the level of IL-6 on POD-1 in L-MCT group was significantly lower than that in the O-MCT group. Conclusion: These results suggested that the surgical stress by L-MCT in patients with poorer hepatic reserve were almost equal to that by O-MCT in patients with relatively good hepatic reserve, indicating the usefulness of L-MCT for HCC patients with poorer hepatic reserve. We recommend the laparoscopic approach for future patients with the criterion that ICGR15 is over 30%.     

Effects of IgM-Enriched Immunoglobulin Therapy in Septic-Shock–Induced Multiple Organ Failure: Pilot Study

Mortality due to septic-shock–induced respiratory failure remains high. A recent meta-analysis suggested that IgM-enriched immunoglobulin treatment may be beneficial in these patients. In this prospective randomised controlled pilot study we investigated the effects of IgM-enriched immunoglobulin treatment in patients with early septic shock accompanied by severe respiratory failure. 33 patients were randomly allocated to receive 5 ml/kg (predicted body weight) IgM-enriched immunoglobulin (16 patients) or placebo (17 patients), respectively, via 8 h IV-infusion for three consecutive days. Daily Multiple Organ Dysfunction Scores (MODS) were calculated. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were monitored daily. For statistical analysis two-way ANOVA was used. Daily MODS showed ongoing multiple system organ failure without significant resolution during the 8 days. Median length of ICU stay, mechanical ventilation, vasopressor support during the ICU stay and 28-day mortality were nearly identical in the two groups. Serum PCT levels showed no significant difference between the two groups, however, CRP levels were significantly lower in the IgM-enriched immunoglobulin group on days 4, 5 and 6, respectively. In this study the use of IgM-enriched immunoglobulin preparation failed to produce any improvement in the organ dysfunction as compared to standard sepsis therapy.     

Transplantation of preconditioned intestinal grafts is associated with lower inflammatory activation and remote organ injury in rats

Reperfused grafts--particularly the intestine--release free radicals and cytokines into the systemic circulation. The type of discharge, which is greatly dependent on the local injury, may also induce inflammatory activation in distant organs and leading to multiple system and organ failure. It has been suggested that intestinal grafts from tacrolimus (TRL)-pretreated donors show improved morphology and microcirculation. We studied whether transplantation of intestines from TRL-pretreated donors influenced inflammatory response and remote organ injury posttransplantation. Donor Sprague Dawley rats received TRL or saline (controls) intravenously at 6 hours prior to graft harvest. The intestinal grafts were preserved in saline for 3 hours before transplantation. At 6 and 12 hours postreperfusion hepatic and renal cortical microcirculation were assessed using laser-Doppler flowmetry (n = 8-12 per group). Blood pressure was measured; liver, kidney, and serum samples were obtained. We analyzed hepatic and renal ICAM-1 expression and caspase-3-like activity as well as plasma content of tumor necrosis factor-alpha and interleukin-6. Pretreated graft recipients had higher mean arterial pressure (82 +/- 10 vs 51 +/- 17 mm Hg, P < .05) and renal perfusion at 6 hours whereas liver perfusion was similar at both 6 and 12 hours. Liver and renal functions were also superior among recipients of pretreated grafts. Both caspase-3-like activity and ICAM-1 expression in liver and kidney were lower in pretreated graft recipients. Plasma IL-6 levels were lower in animals receiving pretreated grafts. Transplantation of intestines from TRL-pretreated donors was followed by a lower systemic inflammatory response, improved organ function and decreased remote injury early posttransplantation compared with animals receiving grafts from untreated donors.     

Clinical evaluation of circulating interleukin-6 and interleukin-10 levels after surgery-induced inflammation

BACKGROUND: It was previously reported that both pro- and anti-inflammatory cytokines are elevated in systemic inflammatory response syndrome (SIRS). Cytokine-mediated systemic neutrophil activation is a direct consequence of SIRS, and can lead to multiple organ dysfunction syndrome (MODS). This prospective study assessed the risk of SIRS and MODS after orthognathic surgery by measuring the circulating levels of inflammatory cytokines such as IL-6 and IL-10 as well as the neutrophil functions as a marker of organ failure. MATERIALS AND METHODS: Blood samples for the measurement of IL-6, IL-10, CRP, neutrophil counts, and neutrophil function were drawn from 21 patients with mandibular prognathism at 2 days before, and at 1 and 3 days after orthognathic surgery. The neutrophil function was estimated by superoxide production and elastase release under the stimulation of FMLP. RESULTS: Eight of the 21 patients were applicable to SIRS criteria 1 day postoperatively, and all of the subjects were excluded from SIRS criteria 3 days postoperatively. Although IL-6 and IL-10 levels were raised 1 day postoperatively, increased cytokine concentrations were decreased in most patients at 3 days postoperatively. The IL-6 concentration and the ratio of IL-6 to IL-10 were higher in the SIRS-matched group compared with the non-SIRS-matched group. Neutrophil priming for superoxide production and elastase release was discovered 1 day after orthognathic surgery, and differences in those values could not be distinguished between the groups. CONCLUSIONS: These results suggest that a few patients in whom high levels of circulating inflammatory cytokine and neutrophil-derived toxic factor continue may have a possibility of contracting severe diseases such as SIRS and MODS after orthognathic surgery. We conclude that the ratio of IL-6 to IL-10 may be a predictive factor in SIRS.     

Comparative study of artifical circulation for the liver after cardiogenic shock: Pulsatile or nonpulsatile?

Because of multiple organ failure (MOF), the survival rate of patients with mechanical circulatery support has not been satisfactory, The purpose of this study is to estimate the effects of pulsatile and nonpulsatile artificial circulation on hepatic microcirculation and function. Cardiogenic shock was induced experimentally by ligating of left anterior descending branch in pigs. For the right ventricular assist device, a nonpulsatile pump (Nikkiso HPM-15) was employed. The left ventricular function was supported by either a nonpulsatile pump (Nikkiso HPM-15: NP group) or a pulsatile pump (Zeon Medical: P group). NP group was further devided into 80% support (NP-1 group) and 100% support (NP-2 group) of the control cardiac output. All groups were maintained at an equivalent mean aortic presure of 3 hours. We measured the hepatic artery blood flow, portal vein flow and hepatic regional blood flow. For the metabolic and hepatic oxygen metabolic data, GOT, GPT, arterial blood ketone body ratio (AKBR), lactate/pirubic acid (L/P), and hyaluronic acid were evaluated. The mean aortic pressure was higher in the NP-2 group than in the other grousp. The hepatic arterial blood flow was significantly higher in the P group than in the others. The AKBR and hepatic oxygen metabolism showed significant improvement in the P group in comparison with others. The regional blood flow in the liver showed improvements in the P and NP-2 groups. These findings suggested that pulsatile circulation may be beneficial for microcirculation of the liver; and the augmented nonpulsatile flow had effects similler to those of pulsatile flow in hepatic circulation.     

Serum interleukin-15 level is a useful predictor of the complications and mortality in severe acute pancreatitis

BACKGROUND: In severe acute pancreatitis, multiple organ dysfunction syndrome and infectious complications are contributors to high mortality. Interleukin (IL)-15 is a novel cytokine that shares many biologic properties with IL-2. Serum IL-15 levels have not yet been determined in SAP. METHODS: Serum IL-15 concentrations were measured in 54 patients with severe acute pancreatitis on admission. The relationships with severity, organ dysfunction, infection, and prognosis were analyzed. Utility of IL-15 for the prediction of clinical outcome was evaluated by receiver operator characteristic (ROC) curve analysis. RESULTS: Serum IL-15 levels were increased significantly in severe acute pancreatitis (5.8 +/- 0.5 pg/mL), and they were correlated with Ranson, APACHE II, and Japanese severity score. Serum IL-15 levels were greater in patients with organ dysfunction, patients with infection, and nonsurvivors (P < 05 each). Incidences of organ dysfunction in patients whose IL-15 levels were less than 3.0, 3.0-5.3, and greater than or equal to 5.3 pg/mL, were 8%, 31%, and 89%, respectively (P < .001). Usefulness of IL-15 for the prediction of organ dysfunction was superior to CRP, IL-6, and IL-8, and it was similar to Ranson, APACHE II, and Japanese severity score. Incidences of infection in patients whose IL-15 levels were less than 5.5, 5.5-9.0, and greater than or equal to 9.0 pg/mL, were 7%, 25%, and 50%, respectively (P < .05). Mortality rates in patients whose IL-15 levels were less than 5.5, 5.5-9.0, and greater than or equal to 9.0 pg/mL, were 11%, 25%, and 80%, respectively (P < .001). Usefulness of IL-15 for the prediction of death was superior to CRP, IL-6, and IL-8. CONCLUSIONS: Serum IL-15 level is a useful predictor of the complications (especially organ dysfunction) and mortality in severe acute pancreatitis.     

微创置管引流对重症急性胰腺炎早期炎症反应的影响

目的:探讨微创置管引流对重症急性胰腺炎(SAP)患者早期炎症反应的疗效。方法:将57例SAP且有腹腔积液患者,采用随机数表法分为微创置管引流治疗组(观察组,29例)和常规治疗组(对照组,28例)。两组均给予相同的基础治疗,观察组给予微创置管引流,对照组给予B超引导下穿刺置管引流。检测两组患者治疗前后TNF-α,IL-6,IL-8及C反应蛋白(CRP)等急性炎症指标,并观察肠道功能恢复时间,全身炎症反应综合征(SIRS)持续时间及多器官功能不全综合征(MODS)的发生率。结果:两组患者均有急性炎症反应发生。两组血清炎症指标术后均不同程度逐渐降低,观察组引流后第3,7天TNF-α,IL-6及CRP的水平与对照组比较明显下降(均P<0.05),而血清IL-8引流后第7天明显低于对照组(P<0.05);观察组肠道功能恢复时间、SIRS持续时间均明显短于对照组的(均P<0.01);观察组MODS发生率(13.8%)也明显低于对照组(28.6%)(P<0.01)。结论:微创置管引流治疗SAP,能明显减轻早期炎症反应,促进肠道功能恢复,降低MODS的发生率。     

Cardiopulmonary bypass elicits a pro- and anti-inflammatory cytokine response and impaired neutrophil chemotaxis in neonatal pigs

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response and organ dysfunction, especially in children. Plasma concentration of inflammatory markers are increased in response to the trauma of cardiac surgery and CPB. The aim of the present study was to investigate whether the CPB procedure in itself elicits increased levels of inflammatory markers in neonatal pigs. METHODS: The inflammatory response was measured in piglets undergoing sternotomy alone (sham group, n=13) or sternotomy and CPB (n=14). Inflammatory mediators were measured at baseline and at fixed time-points during and after CPB. IL-8, IL-10 and TNF-alpha levels and C-reactive protein (CRP) concentrations were measured in plasma samples. Polymorphonuclear neutrophils (PMN) chemotaxis was measured ex vivo, and CD-18 expression using an immunofluorescence technique. RESULTS: Immediately after the CPB procedure increased IL-8 levels were found in the CPB group, but not in sham operated animals (P=0.005). Simultaneously, a marked IL-10 response was measured in the CPB group. Concurrently, PMN chemotaxis decreased in CPB animals but not in the sham group (P=0.04). CD-18 expression and CRP levels were not significantly different between groups and TNF-alpha showed no changes in either group. The chemotactic response did not correlate with plasma IL-8 or IL-10, nor with CD-18 expression. CONCLUSION: The CPB procedure elicited a systemic inflammatory response in terms of significantly elevated plasma levels of IL-8 and IL-10. Furthermore, a temporary and simultaneous decrease in PMN chemotaxis was observed immediately after CPB.     

股肌下结合微斜切入路与经股肌入路全膝关节置换术后早期血清学标志物水平差异

背景:微创全膝关节置换术(TKA)目前仍存在争议,血清肌肉损伤和炎性标志物水平的测定为评估手术创伤提供了一种客观的方法。目的:比较股肌下结合微斜切(SMOC)入路与经股肌入路TKA术后早期反映肌肉损伤和炎症的相关血清学标志物水平的变化,为临床手术方式的比较和选择提供参考。方法:从2018年7~11月拟行TKA的587例患者中,选择63例,按照随机数字表法分为SMOC入路组(n=31)和经股肌入路组(n=32),分别采用SMOC入路、经股肌入路。术中记录两组患者手术切口长度、手术时间、失血量、输血人数。术后1、2、3 d复查血清肌酸激酶(CK)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平。记录术后两组患者可直腿抬高时间,术后3 d髌上5 cm周径、疼痛视觉模拟(VAS)评分,术后4周疼痛VAS评分、美国膝关节协会评分(KSS)、胫骨股骨机械轴夹角(MFTA)和髌股适合角(CA),并进行比较。结果:SMOC入路组患者手术切口长度小于经股肌入路组患者,且差异有统计学意义(P<0.001)。与经股肌入路组患者比较,SMOC入路组患者术后3 d髌上5 cm周径更小,可直腿抬高时间更短,术后3 d、术后4周疼痛VAS评分均更低,术后4周KSS评分更高,术后追加镇痛患者比例更低,且差异均有统计学意义(P均<0.001)。术前两组患者CK、CRP、TNF-α、IL-1β、IL-6水平差异无统计学意义。术后血清CK、CRP水平均较术前升高,且SMOC入路组患者术后1 d、2 d、3 d各时间点血清CK、CRP水平均低于经股肌入路组患者,且差异均有统计学意义(P均<0.001);术后血清TNF-α、IL-1β、IL-6水平均与术前差别不大,且两组患者术后1 d、2 d、3 d各时间点血清TNF-α、IL-1β、IL-6水平差异均无统计学意义。结论:SOMC入路所造成的肌肉损伤和炎症反应明显少于经股肌入路,可加快围手术期康复。     

Hemofiltration for hyperbilirubinemia after left ventricular assist system implantation: Report of four cases

We hypothesized that the use of hemofiltration (HF) to reduce cytokines may attenuate the hyperbilirubinemia that often develops after left ventricular assist system (LVAS) implantation. Four patients with hyperbilirubinemia after LVAS implantation underwent HF continuously for 7 days. Blood samples were collected and the serum concentrations of total bilirubin (T-Bil), interleukin (IL)-6, and IL-8 were measured. We also measured the serum concentrations of IL-6 and IL-8 in the blood flowing into and out of the filter. Two patients had reduced serum concentrations of IL-6, IL-8, and T-Bil, but the other two did not, despite the effective filtration of these cytokines. Our findings suggest that the reduction of cytokines by HF may assist in the treatment of hyperbilirubinemia after LVAS placement in some patients.     

C reactive protein in patients with chronic renal diseases

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53+/-5.8 years with a mean creatinine clearance (C(Cr)) of 52+/-37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0+/-4.6 mg/L and 5.8+/-5.6 pg/mL, respectively and were not significantly correlated (r=0.11, p=n.s.). CRP and IL-6 were however related with renal function (CRP versus C(Cr) r=-0.40 p <0.001; IL- 6 versus C(Cr) r=-0.45; p <0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4+/-6.3 mg/L in the group of patients with a C(Cr) lower than 20 mL/min (n=32) and 2.76+/-4.35 in the group of patients with a C(Cr) higher than 20 mL/min (n = 70) (p <0.0001). CRP and IL-6 were positively related with ESR (r=0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2+/-0.4 versus 3.0+/-0.5 g/dL). CRP and serum albumin were not significantly related (r=0.17). CRP and IL-6 correlated positively with ESR (r=0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation - even in the predialysis phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.     

老年颈动脉硬化患者血清C反应蛋白测定及意义

目的:探讨 C 反应蛋白(C-reactive protein,CRP)作为系统性炎症因子在老年人颈动脉硬化中的改变及其意义。方法:选取经超声多普勒确诊的颈动脉硬化病人共130例,根据狭窄程度分为重组54例,轻组76例,对照组为经超声多普勒证实无颈动脉硬化病变的健康人,共45例。采用放射比浊法测定血清 CRP、放射免疫法测定血清白细胞介素-6(IL-6)浓度。结果:颈动脉硬化组血清 CRP 水平显著高于对照组(P<0.01);在颈动脉硬化患者中,重组血清 CRP 水平显著高于轻组(P<0.01),但两组间 IL-6浓度无显著差异(P>0.05)。结论:血清 CRP、IL-6水平在颈动脉硬化患者中明显升高,CRP 浓度与颈动脉狭窄程度密切相关。     

红花黄色素对早期糖尿病肾病患者hs-CRP、IL-8的影响

目的:探讨红花黄色素(soor yellow,SY)对早期糖尿病肾病(diabetic nephropathy,DN)患者血清细胞因子的影响。方法:将60例早期DN患者随机分为对照组(30例)和治疗组(30例),对照组采用常规西医基础治疗,治疗组在此基础上加用SY。采用酶联免疫吸附法(ELISA)测定两组患者治疗前及治疗30d后血清白细胞介素-8(Interleukin-8,IL-8)、高敏CRP(high sensitive CRP,hs-CRP)表达水平,并检测治疗前、后空腹血糖(fasting blood glucose,FBG)和尿微量白蛋白排泄率(urinary albumin excretion rate,UAER)水平。结果:治疗30d后,对照组和治疗组患者血清FBG水平与治疗前血清FBG水平比较下降,差异有统计学意义(P<0.01),但对照组治疗30d后IL-8、hs-CRP、UAER水平无明显降低,与治疗前比较差异无统计学意义(P>0.05);治疗组使用SY治疗30d后与治疗前比较IL-8、hs-CRP、UAER水平均明显下降,差异有统计学意义(P<0.01),而且治疗组与对照组治疗后比较IL-8、hs-CRP、UAER明显下降,差异有统计学意义(P<0.01)。结论:红花黄色素可减低早期DN患者血清IL-8、hs-CRP的表达,抑制炎症反应,降低尿白蛋白,起到了对早期DN患者的肾脏保护作用。     

Inflammatory markers in patients with severe burn injury: What is the best indicator of sepsis?

OBJECTIVE: To estimate the diagnostic value of serum PCT, CRP, leukocyte count and temperature as markers of sepsis in critically ill ICU burn patients. DESIGN AND SETTING: Prospective, observational study in a four bed Burn Intensive Care Unit. PATIENTS: Forty-three patients admitted in a Burn ICU were included in our study. MEASUREMENTS AND RESULTS: Serum PCT, CRP concentrations, WCC (white cell count), neutrophils and temperature were measured within the first 24h after-burn and daily thereafter. Severity of organ failure was estimated by sequential organ failure assessment (SOFA) score. Every day we classified all patients in one of the following three categories: non-systemic inflammatory condition (non-SIRS), SIRS non-infected and SIRS 2 infected or sepsis. Patients with infected SIRS differ significantly from non-infected SIRS in PCT (11.8+/-15.8 versus 0.63+/-0.0.43, respectively, p < 0.001). On the other hand, WCC, temperature and neutrophils did not differ significantly between patients with SIRS non-infected and infected SIRS. CRP was elevated in all three groups but didn't differ significantly between SIRS non-infected and septic patients. Area under receiver operating curves was 0.975 and showed reasonable discriminative power (p = 0.002, 95% CI, 0.91-1.035) in predicting of sepsis only for PCT. CONCLUSIONS: Serum procalcitonin levels can be used as an early indicator of septic complication in patients with severe burn injury.     

C REACTIVE PROTEIN IN PATIENTS WITH CHRONIC RENAL DISEASES

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53 ± 5.8 years with a mean creatinine clearance (C_Cr) of 52 ± 37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0 ± 4.6 mg/L and 5.8 ± 5.6 pg/mL, respectively and were not significantly correlated (r = 0.11, p = n.s.). CRP and IL-6 were however related with renal function (CRP versus C_Cr r = ?0.40 p < 0.001; IL-6 versus C_Cr r = ?0.45; p < 0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4 ± 6.3 mg/L in the group of patients with a C_Cr lower than 20 mL/min (n = 32) and 2.76 ± 4.35 in the group of patients with a C_Cr higher than 20mL/min (n = 70) (p < 0.0001). CRP and IL-6 were positively related with ESR (r = 0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2 ± 0.4 versus 3.0 ± 0.5 g/dL). CRP and serum albumin were not significantly related (r = 0.17). CRP and IL-6 correlated positively with ESR (r = 0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation – even in the predialysis phase of renal failure – of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.     

Antioxidative resuscitation solution prevents leukocyte adhesion in the liver after hemorrhagic shock.

BACKGROUND: The generation of iron-dependent toxic oxygen radicals during the initial resuscitation from hemorrhagic shock was shown to be a relevant factor for the initiation of the inflammatory cascade. Therefore, this experimental study was designed to evaluate the effects of a deferoxamine-conjugated hydroxyethyl-starch solution (HES-DFO) on oxygen radical induced injury and microcirculatory alterations in the rat liver compared with resuscitation with regular hydroxyethyl-starch, lactated Ringer's solution (RL), or a gelatin-based solution. METHODS: After hemorrhage and random assignment to 1 hour of blood-free resuscitation with the aforementioned solutions, hepatic microcirculation and leukocyte adhesion characteristics were assessed by intravital fluorescence microscopy in anesthetized rats. Oxygen radical activity was estimated by determination of glutathione levels in liver homogenate and determination of thiobarbituric acid-reactive substances in plasma as markers of lipid peroxidation. RESULTS: Resuscitation by HES-DFO resulted in restoration of hemodynamic parameters compared with gelatin-based solution and HES. The hepatic microcirculation was severely altered 1 hour after resuscitation from shock in all groups indicated by sinusoidal narrowing and reduced sinusoidal blood flow. HES-DFO, however, attenuated leukocyte adhesion and improved velocity index in sinusoids as well as sinusoidal perfusion. The shock-associated generation of oxygen radicals during resuscitation was prevented by HES-DFO as indicated by restored glutathione and reduced thiobarbituric acid-reactive substances. CONCLUSION: The results suggest that HES-DFO effectively reduces oxygen radical formation during the initial resuscitation period, thus, attenuating pathologically enhanced leukocyte adhesion and improving hepatic microcirculation.     

Extracorporeal Life Support Bridge to Ventricular Assist Device: The Double Bridge Strategy

In patients requiring left ventricular assist device (LVAD) support, it can be difficult to ascertain suitability for long‐term mechanical support with LVAD and eventual transplantation. LVAD implantation in a shocked patient is associated with increased morbidity and mortality. Interest is growing in the utilization of extracorporeal life support (ECLS) as a bridge‐to‐bridge support for these critically unwell patients. Here, we reviewed our experience with ECLS double bridging. We hypothesized that ECLS double bridging would stabilize end‐organ dysfunction and reduce ventricular assist device (VAD) implant perioperative mortality. We conducted a retrospective review of prospectively collected data for 58 consecutive patients implanted with a continuous‐flow LVAD between January 2010 and December 2013 at The Alfred Hospital, Melbourne, Victoria, Australia. Twenty‐three patients required ECLS support pre‐LVAD while 35 patients underwent LVAD implantation without an ECLS bridge. Preoperative morbidity in the ECLS bridge group was reflected by increased postoperative intensive care duration, blood loss, blood product use, and postoperative renal failure, but without negative impact upon survival when compared with the no ECLS group. ECLS stabilization improved end‐organ function pre‐VAD implant with significant improvements in hepatic and renal dysfunction. This series demonstrates that the use of ECLS bridge to VAD stabilizes end‐organ dysfunction and reduces VAD implant perioperative mortality from that traditionally reported in these “crash and burn” patients.