Correlation between serum IL-6 and CRP levels and severity of head injury in children

Objective: To examine interleukin-6 (IL-6) and C-reactive protein (CRP) release in children with head injury (HI) and investigate if there is a correlation between the levels of these two proteins and the severity of HI. Design: Prospective clinical investigation. Setting: Eight-bed paediatric intensive care unit in a university hospital. Patients: Forty-five children were followed up for 4 days after HI and their serum IL-6 and CRP levels were measured. Measurements and results: Peak serum IL-6 levels occurred 4 h post-injury, decreasing over time. CRP was normal 4 h after injury, then increased reaching peak levels in 48 h. Children with admission Glasgow Coma Scale (GCS) scores of 8 or less had higher IL-6 levels compared to children with GCS scores higher than 8, 4 and 12 h post-injury (p < 0.01 and p < 0.05, respectively). IL-6 was higher in children with admission PRISM scores of 10 or more than in those with PRISM scores lower than 10 at 4 and 12 h (p < 0.05). CRP levels were higher in patients with GCS scores of 8 or less compared to patients with GCS scores higher than 8 at 24, 48 and 72 h (p < 0.05, p < 0.02 and p < 0.02, respectively) . Patients with PRISM scores of 10 or more had higher CRP levels compared to those with PRISM scores lower than 10 at 24, 48 and 72 h (p < 0.05). Peak CRP levels correlated well with peak IL-6 levels (r = 0.49, p < 0.001). No correlation between IL-6 or CRP levels and mortality or clinical outcome was found. Conclusions: Serum IL-6 and CRP levels are elevated in children with HI and there is a relation between the severity of HI and the levels of these proteins. There was no correlation between IL-6, CRP and outcomes of the patients. Received: 30 June 1998 Accepted: 29 October 1998     

Effect of training and strict guidelines on the reliability of risk adjustment systems in paediatric intensive care

Objective Many risk-adjustment systems have significant interobserver variability in everyday clinical practice. This can be partly corrected by strict guidelines and training. These issues have not been well studied in the paediatric setting. We assessed the reliability of two widely used paediatric scoring systems, the Paediatric Risk of Mortality (PRISM) and Paediatric Index of Mortality (PIM), before and after a special training program.Design Prospective observational multi-centred cohort study.Intervention Twenty-seven physicians from five paediatric intensive care units (PICUs) assessed severity of illness in 20 selected patients using PRISM and PIM scores before and after a special training program. Physicians were divided according to level of PICU experience: intensivists (>3 years experience, n=12), fellows (6–30 months experience, n=6) and residents (<6 months experience, n=9). Intraclass correlation was used to compare scoring reliability before and after training.Measurements and results Wide variability in PRISM and PIM scoring was observed before training (intraclass correlation for PRISM scores 0.24–0.73, intraclass correlation for PIM scores 0.16–0.33). Training and implementation of guidelines led to significant increases in interobserver agreement (intraclass correlation 0.74–0.86 for PRISM and 0.88–0.95 for PIM scores), although some variability remained.Conclusion Our results show that the reliability of PRISM and PIM risk adjustment systems in daily clinical practice is much lower than expected. Training and guidelines can significantly increase interobserver agreement. These factors should be taken into account when using these systems for benchmarking, or to compare quality of care between different PICUs.     

Plasma atrial natriuretic peptide and brain natriuretic peptide are increased in septic shock: impact of interleukin-6 and sepsis-associated left ventricular dysfunction

Objective Interest has recently focused on the use of neurohormonal markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) as indices of left ventricular systolic dysfunction and prognosis in heart failure. Also, peptides belonging to the interleukin-6 (IL-6) family have been shown to induce ANP and BNP secretion. We hypothesized that BNP and ANP spillover in the peripheral circulation reflects left ventricular dysfunction and IL-6 production in septic shock.Design and setting Retrospective, clinical study in the medical intensive care unit of a university hospital.Patients and participants 17 patients with septic shock and 19 control subjects.Interventions Collection of clinical and demographic data in relation to ANP, BNP, IL-6, and soluble TNF receptors (sTNF-R-p55, sTNF-R-p75) in plasma over a period of 4 days.Measurements and results In septic shock we found a significant increase in ANP (82.7±9.9 vs. 14.9±1.2 pg/ml) and BNP (12.4±3.6 vs. 5.5±0.7 pg/ml). Plasma ANP peaked together with IL-6. Peaks of ANP and IL-6 were significantly correlated (r=0.73; p<0.01). BNP was inversely correlated to cardiac index (r=–0.56; p<0.05).Conclusions ANP and BNP increase significantly in patients with septic shock. BNP reflects left ventricular dysfunction. ANP is related to IL-6 production rather than to cardiovascular dysfunction.     

Comparative effects of early randomized immune or non-immune-enhancing enteral nutrition on cytokine production in children with septic shock

Objective To compare the effect of early enteral feeding using immune-enhancing (IE) vs. non-immune-enhancing (NIE) formulas on cytokines in children with septic shock.Design and setting A single-center, randomized, blinded controlled trial in a pediatric intensive care unit of a university hospital.Patients We randomized 38 patients with septic shock to either IE or NIE. Feedings were advanced to a target volume of energy intake equal to 1/2, 1, 5/4, 6/4, and 6/4 of the predicted basal metabolic rate on days 1–5, respectively.Measurements and results Interleukins (IL) 1, 6, and 8, tumor necrosis factor , C-reactive protein, Pediatric Risk of Mortality (PRISM) score, survival, secondary infections, length of stay, and mechanical ventilation were compared within and between the two groups. Actual mean energy and protein intakes did not differ between the two groups and the caloric-protein balance was not correlated to cytokine levels. On day 5 IL-6 levels were significantly lower (11.8±2.4 vs. 38.3±3.6) and IL-8 significantly higher in the IE than in the NIE group (65.4±17 vs. 21±2.5). After 5 days of nutritional support a significant decrease in IL-6 levels was recorded only in group IE (mean of paired differences 39.4±3 pg/ml). In multivariate regression analysis the variation in cytokines was independently correlated only to PRISM (R²=–0.50), but pediatric intensive care unit outcome endpoints did not differ between the two groups.Conclusions Early IE nutrition may modulate cytokines in children with septic shock, but there is no evidence that this immunomodulation has any impact on short-term outcome.     

Post-operative circulating cytokine patterns — the influence of infection

Objective To study post-operative plasma concentrations of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) in infected and non-infected patients.Design Prospective controlled clinical study.Setting The intensive care unit (ICU) of a university hospital.Patients and participants The study comprised 20 patients, 9 infected and 11 non-infected, consecutively admitted to the ICU after moderate or major surgery. Twelve healthy volunteers were used as controls.Measurements and results Leucocyte count, CRP and the plasma TNF, IL-1 and IL-6 concentrations were studied 24–48h after the start of surgery. Axillary temperature, the duration of surgery, the number of packed red cells transfused, the APACHE II score and outcome were registered. Both infected and non-infected patients had higher plasma concentrations of IL-6 than the controls (p<0.001 andp<0.01 respectively). Patients with infection had a higher plasma IL-6 concentration than non-infected patients (p<0.05). Similar analyses of plasma TNF concentrations revealed no differences between infected and non-infected patients. Plama IL-1 was detected only occasionally. Non-survivors (n=4) had higher plasma concentrations of TNF and IL-6 than survivors (p<0.05 andp=0.05 respectively). In non-infected patients a correlation between the number of units of packed red cells transfused and the plasma IL-6 concentration was observed (r=0.73,p<0.05).Conclusion No specific plasma cytokine pattern for infected patients subjected to surgery was observed. The effect of surgery and infection on the plasma IL-6 concentration seemed to be additive. Transfusion of packed red cells appeared to elevate the post-operative plasma IL-6 concentration.     

Relationship between sarcopenic obesity-related phenotypes and inflammatory markers in postmenopausal women

Ageing is associated with changes in body composition that may result in sarcopenic obesity (SO). Interleukin-6 (IL-6) and C-reactive protein (CRP) are important inflammatory markers related to ageing. SO has been examined as an important public health problem, but its association with inflammatory markers has yet to be investigated. The aim of this study was to investigate the association between SO-related phenotypes and inflammatory markers in postmenopausal women. A total of 130 women (66·7 ± 5·2 years) underwent body composition evaluation using dual-energy X-ray absorptiometry. Volunteers were classified according to a SO definition previously described in the literature. Waist circumference (WC) and handgrip strength (HG) were also measured. Blood samples were collected for CRP, tumour necrosis factor and IL-6 measurements. All the inflammatory markers were higher in SO individuals when compared to non-SO; however, only IL-6 reached statistical significance (median 3·34 versus 1·37 pg ml⁻¹; P<0·05). Also, CRP was significantly correlated (P<0·01) with body mass index (r_s = 0·34), fat mass (FM; r_s = 0·25) and WC (r_s = 0·33). Similarly, IL-6 levels were significantly correlated (P<0·05) to age (r_s = 0·19), FM (r_s = 0·19) and WC (r_s = 0·17). HG was found to be significantly reduced among subjects with higher IL-6 levels (P = 0·02). In summary, the combination of reduced muscle mass and excess body fat (i.e. SO) is associated with elevated inflammatory markers in postmenopausal women. Moreover, CRP and IL-6 are associated with SO-related phenotypes in this population.     

Delivery dependent oxygen consumption in patients with septic shock: Daily variations,relationship with outcome and the sick-euthyroid syndrome

Delivery dependent oxygen consumption (DDOC) is observed in patients with sepsis and vital organ dysfunction, and has been related to outcome. Similarly the sick-euthyroid syndrome is associated with a high mortality. We examined the daily variations of DDOC and its relation to hormonal changes, particularly those of the thyroid. In 22 patients, 14 with septic shock and 8 post-operative controls, oxygen delivery was increased by increasing cardiac output with vasodilation by phentolamine, during a total of 207 days. DDOC varied markedly between consecutive days in individual patients with sepsis, in both survivors and non-survivors. DDOC was related to severity of illness, assessed by APACHE II score (r=0.50,p=0.017), and plasma levels of triiodothyronine (T₃),r=–0.49,p=0.011, and thyroxine (T₄),r=–0.53,p=0.012. No correlation was observed between DDOC and outcome, nor blood levels of lactate, epinephrine, norepinephrine, dopamine or cortisol. In conclusion, we observed a marked disturbance of systemic oxygen uptake autoregulation in patients with septic shock which varied during the clinical course and was related to the sick-euthyroid syndrome.With the technical assistance of J. Lopez     

Influence of pentoxifylline on cytokine levels and inflammatory parameters in septic shock

Objective To evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock.Design Prospective study comparing a therapy group to a matched control group.Setting Medical intensive care unit at a university hospital.Patients Twenty four patients fulfilling the criteria of septic shock were included in this study. Twelve patients received PTX (therapy group) and 12 patients matched for diagnosis, age and gender served as the control group.Interventions Pentoxifylline at 1 mg/kg per hour over 24 h in the therapy group.Measurements ad results Cytokine levels [tumor necrosis factor- (TNF)], soluble TNF receptor [TNF-R], and interleukin-6 [IL-6] and inflammatory proteins [C-reactive protein, -1-antitrypsin (AAT), fibronectin, and haptoglobin], as well as hemodynamic parameters and the APACHE III score were evaluated before initiation of therapy and 24 h later. After 24 h, TNF levels were significantly lower in the therapy group (p=0.013), while IL-6 levels were significantly higher in the therapy group (p=0.030). Within the 24 h TNF declined significantly in the therapy group (p=0.006), while IL-6 showed a significant increase (p=0.043). AAT and the APACHE III score tended to differ significantly after 24 h between the groups [AAT levels higher in the therapy group (p=0.05), APACHE III score lower (p=0.05)]. In the therapy group, the systemic vascular resistance index was significantly higher after 24 h (p=0.0026) whereas the cardiac index declined (p=0.035).Conclusions PTX does influence TNF levels in septic shock patients. Nevertheless, inhibiting a single mediator in severe septic shock cannot stop the inflammatory overreaction.     

Effect of anesthesia and surgery on plasma cytokine levels

Cytokines released in response to stress may have a profound impact on circulatory stability. There is no information on the effect of general anesthesia alone on plasma cytokine levels and little information on cytokine release following surgery. Plasma cytokine levels and hemodynamic parameters were measured during anesthesia and abdominal surgery under sterile and nonpyrogenic conditions in seven pigs anesthetized with ketamine and pentobarbital. Tumor necrosis factor (TNF) was measured by bioassay. Bioassays of low and high sensitivity were used to measure interleukin 6 (IL-6). Measurements were made sequentially during: (1) 4 hours observation with anesthesia alone; (2) 2 hours following laparotomy and traumatic intestinal manipulation (IM) sufficient to produce shock; and (3) after an intravenous bolus of 1 μg/kg endotoxin as a positive control. Arterial blood pressure decreased following IM from 91.5 ±- 5.8 to 48.6 ±- 3.2 mm Hg, (mean ±- SE, P < .05), with no further change following endotoxin. Heart rate was unchanged during the experiment, and central venous pressure decreased after endotoxin (P < .05). There were no increases in TNF or IL-6 (using a low sensitivity assay) with anesthesia alone or following IM with shock, but both increased after endotoxin administration (P < .05); using a high sensitivity assay, IL-6 did not change during anesthesia alone but did increase fivefold following IM with shock (P < .05) and 50-fold following endotoxin administration (P < .05). We conclude that in a porcine model under sterile and nonpyrogenic conditions, prolonged anesthesia does not increase plasma cytokine levels. Traumatic manipulation of the intestines sufficient to cause diffuse bowel injury and shock causes only small increases in plasma IL-6. Substantial increases in both TNF and IL-6 occur following a minimal endotoxin challenge showed an intact functional systemic response.     

Changes in muscle tissue oxygenation during stagnant ischemia in septic patients

Objective To determine changes in the rate of thenar muscles tissue deoxygenation during stagnant ischemia in patients with severe sepsis and septic shock.Design and setting Prospective observational study in the medical ICU of a general hospital.Patients and participants Consecutive patients admitted to ICU with septic shock (n=6), severe sepsis (n=6), localized infection (n=3), and healthy volunteers (n=15).Interventions Upper limb ischemia was induced by rapid automatic pneumatic cuff inflation around upper arm.Measurements and results Thenar muscle tissue oxygen saturation (StO₂) was measured continuously by near-infrared spectroscopy before and during upper limb ischemia. StO₂ before intervention was comparable in patients with septic shock, severe sepsis, or localized infection and healthy volunteers (89 [65, 92]% vs. 82 [72, 91]% vs. 87 [85, 92]% vs. 83 [79, 93]%, respectively; p>0.1). The rate of StO₂ decrease during stagnant ischemia after initial hemodynamic stabilization was slower in septic shock patients than in those with severe sepsis or localized infection and in controls (–7.0 [–3.6, –11.0] %/min vs. –10.4 [–7.8, –13.3] %/min vs. –19.5 [–12.3, –23.3] vs. –37.4 [–27.3, –56.2] %/min, respectively; p=0.041). At ICU discharge the rate of StO₂ decrease did not differ between the septic shock, severe sepsis, and localized infection groups (–17.0 [–9.3, –28.9] %/min vs. –19.9 [–13.3, –23.6] %/min vs. –23.1 [–20.7, –26.2] %/min, respectively), but remained slower than in controls (p<0.01). The rate of StO₂ decrease was correlated with Sequential Organ Failure Assessment (SOFA) score (r=0.739, p<0.001).Conclusions After hemodynamic stabilization thenar muscle tissue oxygen saturation during stagnant ischemia decreases slower in septic shock patients than in patients with severe sepsis or localized infection and in healthy volunteers. During ICU stay and improvement of sepsis the muscle tissue deoxygenation rate increases in survivors of both septic shock and severe sepsis and was correlated with SOFA score.     

Characteristics and immediate outcome of childhood meningitis treated in the pediatric intensive care unit

Objective To describe patient characteristics, use of technology and mortality in children with meningitis admitted to the pediatric intensive care unit (PICU).Design Retrospective cohort study.Setting Fifteen US PICUs.Patients All admissions with a diagnosis of meningitis between 1995 and 2000 in the Pediatric Intensive Care Unit Evaluations (PICUEs) database.Measurements and results Of 559 patients with meningitis, 58% were male. The median age was 19 months and the median length of PICU stay was 2 days. The crude PICU mortality rate was 7%. Three hundred thirty-four (60%) patients had bacterial meningitis. Non-survivors had significantly higher Pediatric Risk of Mortality (PRISM) III scores and also constituted a larger proportion of the patients with bacterial meningitis, coma and shock upon PICU admission. The use of invasive devices was higher among non-survivors, patients with bacterial meningitis or those who were in coma or shock upon PICU admission. There was significant variation in the use of intracranial pressure (ICP) monitors by coma status and by institution. In multivariate analysis, patients had 1.26 higher odds of mortality for each unit increase in PRISM III score (odds ratio 1.26, 95% confidence interval: 1.19–1.34), while adjusting for other variables.Conclusion In a large cohort of children admitted to the PICU with meningitis, severity of illness, particularly the presence of shock or coma, was significantly associated with both the higher use of invasive medical devices and higher mortality. There was significant variation in the use of ICP monitors among the various PICUs without statistical association with survival.Presented, in part, at the 14^th Pediatric Critical Care Colloquium, San Diego, CA, USA, October 2002     

Pro-inflammatory cytokine release and mediation of the acute phase protein response in fulminant hepatic failure

Objective: To study the relationship between interleukin-6 (IL-6), tumour necrosis factor (TNF) and the acute phase protein C-reactive protein (CRP) in patients with fulminant hepatic failure (FHF) and to investigate the potential of peripheral blood mononuclear cells (PBMC) isolated from these patients to stimulate CRP production by isolated human hepatocytes in vitro. Setting: Patients with FHF were studied at the time of their admission to the intensive care unit. Study design: Serum TNF and IL-6 were measured in 12 patients with FHF. PBMC from 6 of these patients were then cultured in the presence and absence of lipopolysaccharides (LPS). TNF and IL-6 in serum and supernatants were measured by ELISA. PBMC supernatants were added to isolated human hepatocytes and CRP production was measured. Results: Serum IL-6 (348 ± 172 pg/ml) and TNF (118.5 ± 15.5 pg/ml) were elevated compared with healthy controls (not detected) and these observations were matched by elevated serum CRP in patients with FHF (38.9 ± 7 mg/l). Both the production of IL-6 and TNF by PBMC isolated from patients with FHF and the potential of supernatants from these cells to stimulate CRP production by hepatocytes in vitro was significantly reduced compared with controls. Conclusions: Despite the observation that patients with FHF have an elevated hepatic acute phase response, PBMC from patients with FHF have reduced potential to produce IL-6 and TNF and elicit an acute phase response in vitro by the time of patient admission to the intensive care unit. One explanation for this observation is early activation and exhaustion of PBMC in vivo. Received: 18 August 1997 Accepted: 13 January 1998     

Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction

Summary. Background: The association of plasma fibrinogen with myocardial infarction (MI) may (like that of C‐reactive protein, CRP) be a marker of subclinical inflammation, mediated by cytokines such as interleukin‐6 (IL‐6). There are well‐recognized discrepancies between commonly performed fibrinogen assays. Increased ratio of clottable fibrinogen to intact fibrinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional fibrinogen, and is elevated in acute MI. Objective: To compare the associations of intact fibrinogen and four routine fibrinogen assays (two von Clauss assays; one prothrombin‐time derived; and one immunonephelometric) in a case–control study of previous MI. Patients/methods: Cases (n = 399) were recruited 3–9 months after their event; 413 controls were age‐ and sex‐ matched from the case–control study local population. Intact fibrinogen was measured in 50% of subjects. Results: All routine fibrinogen assays showed high intercorrelations (r = 0.82–0.93) and significant (P < 0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact fibrinogen (r = 0.45–0.62), while intact fibrinogen showed only a small, nonsignificant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact fibrinogen assay was significantly higher (P < 0.0003) in cases vs. controls. Each fibrinogen assay correlated with plasma levels of CRP and IL‐6 (which were also elevated in cases vs. controls). Each routine fibrinogen assay remained significantly elevated in cases vs. controls after further adjustment for C‐reactive protein and interleukin‐6. Conclusions: These data provide evidence for acquired, increased hyperfunctional plasma fibrinogen in MI survivors, which is not associated with markers of inflammatory reactions. The causes and significance of these results remain to be established in prospective studies.     

Procalcitonin (PCT) is useful in predicting the bacterial origin of an acute circulatory failure in critically ill patients

Objective To evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection in ICU medical and surgical patients. Setting A 10-bed medical surgical unit. Design PCT, C-reactive protein (CRP), interleukin 6 (IL-6) dosages were sampled in four groups of patients: septic shock patients (SS group), shock without infection (NSS group), patients with systemic inflammatory response syndrome related to a proven bacterial infection (infect. group) and ICU patients without shock and without bacterial infection (control group). Results Sixty patients were studied (SS group:n=16, NSS group,n=18, infect. group,n=16, control group,n=10). The PCT level was higher in patients with proven bacterial infection (72±153 ng/ml vs 2.9±10 ng/ml,p=0.0003). In patients with shock, PCT was higher when bacterial infection was diagnosed (89 ng/ml±154 vs 4.6 ng/ml±12,p=0.0004). Moreover, PCT was correlated with severity (SAPS:p=0.00005, appearance of shock:p=0.0006) and outcome (dead: 71.3 g/ml, alive: 24.0 g/ml,p=0.006). CRP was correlated with bacterial infection (p<10⁻⁵) but neither with SAPS nor with day 28 mortality. IL-6 was correlated with neither infection nor day 28 mortality but was correlated with SAPS. Temperature and white blood cell count were unable to distinguish shocked patients with or without infection. Finally, when CRP and PCT levels were introduced simultaneously in a stepwise logistic regression model, PCT remained the unique marker of infection in patients with shock (PCT≥5 ng/ml, OR: 6.2, 95% CI: 1.1–37,p=0.04). Conclusion The increase of PCT is related to the appearance and severity of bacterial infection in ICU patients. Thus, PCT might be an interesting parameter for the diagnosis of bacterial infections in ICU patients.     

Topical interleukin-8 antibody attracts leukocytes in a piglet lavage model

Objective Acute respiratory distress syndrome (ARDS) in young infants is linked with a pulmonary inflammatory response part of which are increased interleukin-8 (IL-8) levels and migration of polymorphonuclear leukocytes (PMNL) into lung tissue. A topical application of an antibody against IL-8 might therefore decrease PMNL migration and improve lung function.Design Randomized, controlled, prospective animal study.Setting Research laboratory of a university childrens hospital.Subjects and interventions Anesthetized, mechanically ventilated newborn piglets (n=22) underwent repeated airway lavage to remove surfactant and to induce lung inflammation. Piglets then received either surfactant alone (S, n=8), or a topical antibody against IL-8 admixed to surfactant (S+IL-8, n=8), or an air bolus injection (control, n=6).Measurements and results After 6 h of mechanical ventilation following intervention, oxygenation [S 169±51 (SD) vs S+IL-8 139±61 mmHg] and lung function (compliance: S 1.3±0.4 vs S+IL-8 0.9±0.4 ml/cmH₂O/kg; extra-vascular lung-water: S 27±9 vs S+IL-8 52±28 ml/kg) were worse in the S+IL-8 group because reactive IL-8 production [S 810 (median, range 447–2323] vs S+IL-8 3485 (628–16180) pg/ml; P<0.05) with facilitated migration of PMNL into lung tissue occurred. Moreover, antibody application caused augmented chemotactic potency of IL-8 [linear regression of migrated PMNL and IL-8 levels: S r²=0.30 (P=ns) vs S+IL-8 r²=0.89 (P=0.0002)].Conclusion Topical anti-IL-8 treatment after lung injury increases IL-8 production, PMNL migration, and worsens lung function in our piglet lavage model. This effect is in contrast to current literature using pre-lung injury treatment protocols. Our data do not support anti-IL-8 treatment in young infants with ARDS.Financial support: supported by Hübner-Stiftung im Stifterverband, Essen; and Deutsche Forschungsgemeinschaft, Bonn, grant KR 1863/1-1     

Blood lactate and mixed venous-arterial PCO2 gradient as indices of poor peripheral perfusion following cardiopulmonary bypass surgry

Conventional indices of tissue perfusion after surgery involving cardiopulmonary bypass (CPB) may not accurately reflect disordered cell metabolism. Venous hypercarbia leading to an increased veno-arterial difference in CO₂ tensions (V-aCO₂ gradient) has been shown to reflect critical reductions in systemic and pulmonary blood flow that occur during cardiorespiratory arrest and septic shock. We therefore measured plasma lactate levels and V-aCO₂ gradients in 10 patients (mean age 57.2 years) following CPB and compared them with conventional indices of tissue perfusion. Plasma lactate levels, cardiac index (CI) and oxygen uptake all increased significantly (p<0.05 vs baseline levels) up to 3h following surgery. Oxygen delivery did not change. Plasma lactate levels correlated significantly with CI (r=0.47,p<0.01). V-aCO₂ fell significantly with time (p<0.01 vs baseline). There was an inverse relationship between V-aCO₂ and cardiac index and V-aCO₂ and lactate (r=–0.37,p<0.05;r=–0.3,p<0.05 respectively). We conclude that blood lactate, CI and increase progressively following CPB. An increase in lactate was associated with a decrease in V-aCO₂. An increase in V-aCO₂ was not therefore associated with evidence of inadequate tissue perfusion as indicated by an increased blood lactate concentration.     

The prognosis of oncologic patients in the pediatric intensive care unit

Objective To evaluate the predicted mortality rate of oncologic patients in the PICU using the PRISM score and factors that might influence short-term outcomes.Design Retrospective study.Setting: Pedriatic ICU in a university hospitalPatients and Methods The medical charts of all oncologic patients admitted to the PICU during the period from January 1983 to December 1992 were reviewed.Main Results Over a period of 10 years, 51 oncologic patients were admitted on 57 occasions to the PICU. The mortality was 32%. This is significantly higher than the overall mortality in the PICU (8%). Comparison of observed and predicted mortality, derived from the PRISM score, using chi square goodness-of-fit tests showed a significantly higher observed mortality (x ²(5)=20.1,P<0.01). Patients admitted for circulatory failure and the highest mortality (47%), followed by those with respiratory failure due to tachypnea/cyanosis (36%), central nervous system deterioration (27%), respiratory failure due to ariway obstruction (25%), and metabolic disorders (20%). Of the 31 patients who needed mechanical ventilation, 17 died (55%), and when they needed inotropic support as well, the mortality increased to 69%. The mortality rose to 100% when the patient was admitted with a septic shock, necessitating mechanical ventilation and inotropic support. The median PRISM score was 5 in the survivor group and 18.5 in the non-survivor group; this difference was found to be significant using the Wilcoxon test (P=0.01). However, some patients with high scores were found in the survivor group, as well as some with low scores in the non-survivor group.Conclusion The decision to treat opcologic patients in a PICU remains difficult and has to be considered on an individual basis. However, oncologic patients do benefit from admission to the PICU. The PRISM score is not suitable for oncologic patients in the PICU, because it underestimates the observed mortality. Other factors like neutropenia, septic shock, the need for mechanical ventilation, and inotropic support should be taken into consideration.     

Circulating lncRNA IFNG‐AS1 expression correlates with increased disease risk,higher disease severity and elevated inflammation in patients with coronary artery disease

Background

This study aimed to investigate the associations of circulating long, non‐coding (lncRNA) IFNG‐AS1, lncRNA ANRIL and lncRNA ITSN1 relative expressions with disease risk, severity and inflammatory cytokines levels in coronary artery disease (CAD) patients.

Methods

One hundred and ninety‐one patients suspected of CAD who underwent coronary angiography were consecutively enrolled in this casecontrol study, and divided into CAD patients (N = 102) and controls (N = 89) according to coronary angiographic results. Blood samples of all participants were collected. Plasma lncRNA IFNG‐AS1, lncRNA ANRIL and lncRNA ITSN1 expressions were detected using quantitative polymerase chain reaction (qPCR). Serum tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β (IL‐1β), IL‐6, IL‐8, IL‐10, and IL‐17 were assessed using enzyme‐linked immunosorbent assay (ELISA). Gensini Score was used to evaluate the disease severity of CAD patients.

Results

LncRNA IFNG‐AS1 relative expression in CAD patients was upregulated compared with that in controls (P < .001), and the receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of lncRNA‐IFNG‐AS1 for predicting the risk of CAD was 0.755 (95% CI: 0.688‐0.821). lncRNA IFNG‐AS1 relative expression was remarkably associated with Gensini Score (r = .259, P = .009). Additionally, lncRNA IFNG‐AS1 relative expression was positively associated with high‐sensitivity C‐reactive protein (hs‐CRP) (r = .283, P = .004), TNF‐α (r = .269, P = .006), and IL‐6 levels (r = .425, P < .001), while it was negatively correlated with IL‐10 level (r = −.263, P = .008). lncRNA ANRIL or lncRNA ITSN1 was not correlated with CA D risk, Gensini Score, hs‐CRP, ESR, TNF‐α, IL‐1β, IL‐6, IL‐8, IL‐10, or IL‐17 levels (all P > .05).

Conclusion

Circulating lncRNA IFNG‐AS1 expression correlates with increased disease risk, higher disease severity and elevated inflammation in CAD patients.

     

Associations between quality of life, fatigue, and cytokine levels in patients aged 50+ with acute myeloid leukemia

Goals of work  Quality of life (QOL) is significantly impaired in patients with acute myeloid leukemia (AML), and fatigue is the most common and disabling symptom; effective treatment measures have yet to be found. Cytokines, biomarkers of inflammation, may moderate both health outcomes, but published data are limited. We looked at the role of cytokines in modulating QOL and fatigue in an older AML population. Patients and methods  We recruited 34 English-speaking patients (23 men, 11 women) aged 50 or older with AML within 1 year of diagnosis. QOL and fatigue were assessed with validated questionnaires. Blood was simultaneously drawn for quantitative measurement of a 13-cytokine panel. Repeat measurements were done 4–6 weeks later (n = 28 patients). Spearman correlations between health measures and cytokine levels were examined at baseline, as were changes in variables between time points. A potentially clinically important correlation was defined as an r ≥ 0.30. Results  At baseline, potentially clinically important correlations were noted between global QOL and interferon (IFN)-γ (r = −0.376, p = 0.031), interleukin (IL)-2 (r = −0.340, p = 0.053), IL-5 (r = −0.368, p = 0.035), IL-8 (r = −0.312, p = 0.077), and TNF-α (r = −0.326, p = 0.064). A similar correlation was observed between IL-6 and fatigue (r = 0.332, p = 0.059). Between time points, there were no potentially important correlations between changes in global QOL and any cytokine. However, potentially important correlations with fatigue were seen with both IL-5 (r = 0.344, p = 0.073) and IL-10 (r = 0.326, p = 0.091) between time points. Conclusions  These preliminary data provide support for a larger controlled study of cytokines, fatigue, and QOL in patients with AML.     

夜间低氧对慢性阻塞性肺疾病患者血清IL-6、IL-8的影响

目的:探讨慢性阻塞性肺疾病(COPD)患者夜间低氧与全身炎症反应的关系。方法:选择中度至极重度COPD患者70例,年龄45～74岁,平均(65.41±7.84)岁。按多导睡眠监测结果将研究对象分为低氧组和非低氧组,均行肺功能和多导睡眠监测、炎症指标检测。比较各组血清IL-6及IL-8的差异,分析炎症指标与睡眠呼吸参数的相关性。结果:睡眠低氧组27例,低氧率为38.57%,低氧组血清IL-6、IL-8分别为(14.34±2.76) ng/mL、(68.49±9.65) ng/mL,明显高于非低氧组的(11.79±1.85) ng/mL、(61.62±8.47) ng/mL(均P0.001)。经校正年龄、体质量指数后,IL-6与睡眠呼吸相关参数TS88正相关(r=0.651,P=0.041),与最低SaO_2和平均SaO_2负相关(r=-0.644,P=0.038和r=-0.780,P=0.018);IL-8与睡眠呼吸相关参数TS88正相关(r=0.627,P=0.039),与最低SaO_2和平均SaO_2负相关(r=-0.659,P=0.026和r=-0.732,P=0.014)。结论:中度至极重度COPD患者夜间低氧普遍存在,低氧组患者全身炎症反应明显增强,全身炎症反应与夜间低氧相关。