Blood interleukin 10 levels parallel the severity of septic shock

The aim of this study was to investigate the relation between interleukin (IL) 10, tumor necrosis factor alpha (TNF), IL-1, and IL-6 levels in patients with septic shock and relate these cytokine levels to the development of organ failure.

In 11 patients with septic shock of recent onset, blood was sampled for determinations of TNF, IL-1, IL-6, and IL-10. The degree of organ failure was scored for four organ systems (respiratory, hepatic, renal, hematologic) in the first 48 hours of the study.

The APACHE II score was 21 ± 4. Three patients died. IL-10 levels were directly correlated with TNF levels (r = 0.73, P < .05) and IL-6 levels (r = 0.67, P < .05); and inversely correlated with total C3 (r = −0.73, P < .05) and CH50 (r = −0.68, P < .05). Both IL-10 and TNF levels were correlated to the organ failure score (r = 0.75 and r = 0.68, both P < .01). Six patients with high IL-10 levels (>60 pg/mL) had lower C3 (37 ± 11 v 62 ± 10 mg/dL) and CH50 (32 ± 7 v 68 ± 19%), and higher organ failure scores (5.7 ± 0.8 v 3.8 ± 1.3) than those with low IL-10 levels (all P < .05).

Although IL-10 has an inhibitory effect on the production of cytokines, it is released together with TNF and IL-6 in patients with septic shock. IL-10 blood levels are directly related to the severity of inflammation and the development of organ failure in septic shock.     

Effects of N-acetylcysteine in endotoxic shock

: The release of oxygen-free radicals has been implicated in both peripheral vascular and myocardial alterations of septic shock. N-Acetylcysteine (N-AC), a substrate for the production of glutathione, has potent antioxidant effects. As a nitrosothiol, it may also improve capillary blood flow. We studied the effects of N-AC in a dog model of endotoxic shock.

: Ten pentobarbital-anesthetized, mechanically ventilated dogs were randomly assigned to receive either N-AC (150 mg/ kg loading dose in 1 hour, followed by 20 mg/kg · h maintenance dose) or D5W. After the loading dose, each dog received 3 mg/kg Escherichia coli endotoxin intravenously. After 30 minutes, saline infusion was started to restore and maintain baseline filling pressures.

: The loading dose of N-AC increased Do₂ significantly (from 661 ± 54 to 914 ± 190 mL/min, P < .05), but Vo₂ remained stable. After the administration of endotoxin, fluid challenge restored cardiac output to baseline, in both groups. Hemoglobin and, thus, Do₂ were slightly lower in the N-AC-treated dogs, but Vo₂ was similar in both groups. At the end of the study, O₂ER was significantly higher in the N-AC-treated dogs than in the control dogs. Blood lactate levels fell more rapidly in the N-AC dogs than in the control dogs. Blood lactate levels returned to normal in the N-AC dogs but not in the control dogs. Tumor necrosis factor (TNF) also decreased significantly in the N-AC dogs but remained elevated in the control dogs.

: These data indicate that N-AC administration in endotoxic shock is well tolerated, may increase oxygen availability to the tissues, and is associated with an attenuation of TNF release.     

Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs

: The lazaroids are a new class of potent free-radical scavengers. We tested whether U-74389G, a lazaroid, could attenuate some of the adverse cardiopulmonary effects of sepsis.

: Dogs were randomized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchange, they were then randomized to receive either 0.2 mg/kg endotoxin or a saline infusion. Measurements of hemodynamics and gas exchange were repeated. The study was concluded 70 minutes after endotoxin infusion and the lungs were then removed for histologic evaluation.

: In endotoxin-treated control animals, P0₂ decreased (278 ± 123 mm Hg to 67 ± 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% ± 1.1% to 28.2% ± 11.4%, P < .05) after endotoxin. Pretreatment with U-74389G attenuated the decrease in PO₂ (476 ± 61 mm Hg to 226 ± 143) and the increase in intrapulmonary shunt (12.6% ± 6.1% to 14.3% ± 6.8%) observed after endotoxin. The extent of lung injury and systemic hemodynamics were similar between control or U-74389G-treated dogs.

: A free-radical-scavenger can attenuate the gas exchange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics.     

Ischemia/reperfusion injury to the ileum does not account for the ileal Vo2-Do2 alterations induced by endotoxin

Endotoxin (lipopolysaccharide [LPS])-induced systemic organ injury leads to disruption of normal systemic organ metabolic processes, which are manifest clinically by signs of accelerated anaerobic metabolism (eg, tissue acidosis and hyperlactatemia) and altered Vo₂-Do₂ relationships. The association of increased anaerobic metabolism with Vo₂-Do₂ alterations has led to the notion that ischemia/reperfusion (I/R) injury may be a prerequisite for the development of Vo₂-Do₂ alterations during endotoxemia. However, in contrast to sepsis, in which oxygen consumption is often increased, oxygen consumption is severely decreased after I/R injury. Based on these observations, we hypothesized that I/R injury would result in systemic organ Vo₂-Do₂ alterations, which are distinct from those that occur in sepsis.

We used the in situ autoperfused feline ileal preparation to simultaneously examine microvascular permeability, reflected as the ileal lymph to plasma protein concentration ratio (C_L/C _P), and ileal Vo₂-Do₂ relationships after either intravenous LPS (2.0 mg/kg; N = 5) or I/R injury (n = 5), and in matching controls (n = 5).

As expected, all LPS-treated and I/R-injured animals were found to have extensive ileal histological damage and marked increases in the C_L/C_P compared with controls (0.315 ± 0.009 and 0.329 ± 0.034, respectively, v 0.097 ± 0.009; P < .001, both comparisons). In addition, the critical Do₂ (Do₂c) was elevated, and the critical oxygen extraction was decreased in both the I/R and LPS groups relative to controls. However, as initially hypothesized, the Vo₂ at the critical Do₂ was markedly decreased in the I/R group compared with that of the LPS group.

These data indicate that I/R injury is insufficient to account for the systemic organ Vo₂-Do₂ alterations that occur with LPS injury.     

Noninvasive assessment of regional albumin extravasation in porcine septic shock

In order to study noninvasively the regional distribution of changes in microvascular albumin flux in septic shock, ¹³¹I human serum albumin and ^98mTc red blood cells were injected IV into anesthetized pigs randomized to receive saline (n = 4) or live E. coli bacteria 3 × 10⁸ × kg⁻¹ IV (n = 8). Images of thorax, abdomen, and left hindlimb were obtained using a gamma camera and a computer. Septic pigs developed pulmonary hypertension and low cardiac output circulatory shock. Hematocrit rose and plasma colloid osmotic pressure fell. Regions of interest were drawn in the ^99mTc images. For each region we calculated an albumin leak index. The albumin leak index over the lungs was higher in sepsis than in controls (1.62 ± 0.42 × 10⁻³ v 0.45 ± 0.05 × 10-3 × min⁻¹, P < .005), even when divided by the pulmonary intravascular filtration pressure, incorporating hydrostatic and colloid osmotic pressures (P < .01). The index was also higher in abdominal regions (for the peripheral abdomen, 6.07 ± 2.98 × 10⁻³ v 0.40 ± 0.72 × 10⁻³ × min⁻¹, P < .005), but not in the hindlimb. In sepsis, the albumin leak index increased more in the abdomen than in the lungs (P < .05). We conclude that in porcine septic shock pulmonary microvascular permeability is increased, but the microvascular albumin flux and thus plasma extravasation increased more in the abdomen than in the lungs.     

Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis

OBJECTIVE: During sepsis, after an initial stimulation immune cells down-regulate their functions, leading to a state of immunosuppression. Because the mechanisms of such down-regulation are unclear, we investigated the hypothesis of an energetic failure of immune cells to participate in immune dysfunction. DESIGN: Cohort of septic shock patients to study peripheral blood mononuclear cells (PBMCs) biological energy in comparison to healthy volunteer cells. SETTING: Critical care unit and laboratory, university hospital. SUBJECTS: Eighteen severe sepsis or septic shock patients and 32 healthy volunteers. INTERVENTIONS: Ex vivo measurement of oxygen consumption in PBMCs taken from patients. The PBMCs' mitochondrial oxidative phosphorylation was investigated using adenosine diphosphate stimulation. The plasma factors implication was tested, using healthy cells incubated in septic plasma, or septic cells incubated in healthy plasma, at different time points of sepsis. The relationship between monocyte human leukocyte antigen-DR expression and bioenergetic results was tested. MEASUREMENTS AND MAIN RESULTS: Baseline oxygen consumption was higher in septic PBMCs (p < .01), with an attenuated response to adenosine diphosphate stimulation (p < .01). Oxygen consumption of healthy PBMCs incubated in septic plasma mimicked the septic cell response, with amplitude depending on the duration of sepsis (days 0-28). Septic cells incubated in healthy plasma partially recovered normal patterns. Septic plasma incubation increased the fraction of decoupling oxygen consumption (p = .021). A relationship between oxygen consumption (baseline or adenosine diphosphate stimulated) and human leukocyte antigen-DR expression was observed for incubation with plasma sampled at different time points of septic shock. CONCLUSION: Energetic failure of PBMCs in sepsis may be a factor associated with the modulation of immune response and human leukocyte antigen-DR phenotype, partially driven by plasma factors.     

Circuit factors in the high cardiac output of sepsis

The increase of cardiac output (CO) in sepsis must be matched by an increase in venous return. Our goal was to determine which of the determinants of venous return are responsible in volume-loaded and nonvolume-loaded pigs with endotoxemia. The determinants include stressed volume, venous compliance (C_v), venous resistance (RVR) and right atrial pressure (Pra). We also tested the effect of the nitric oxide (NO) synthase inhibitor, N^ω-nitro- -arginine-methyl ester (L-NAME) after the hemodynamics with endotoxin stabilized.

Pigs were anesthetized and mechanically ventilated. We measured CO by thermodilution, mean circulatory filling pressure (MCFP) by inflating a balloon in the right atrium, blood volume by dye dilution, and C_v by rapid blood infusions. RVR was calculated from MCFP - Pra/CO). After baseline measurements, we infused 10 μg/(kg x h⁻¹) of Escherichia coli endotoxin. Eight animals also received 30 mL × kg⁻¹ of dextran over the 2 hours (volume treated), and seven did not (no volume). After 2 hours we injected 25 mg × kg⁻¹ of the NO synthase inhibitor, L-NAME, and repeated the measurements.

In volume-treated animals, CO increased from 3.9 ± 0.7 to 5.4 ± 0.8 L x min⁻¹ (P < .05), and blood pressure (BP) fell from 118 ± 9 to 76 ± 12 mmHg. MCFP rose, and there was no change in RVR or C_v, whereas capacitance increased (ie, right shift of pressure-volume curve). Cardiac function (ie, Starling curve) did not change. In no-volume animals, CO fell from 4.47 ± 0.64 to 2.50 ± 0.86 L × min⁻¹, BP from 114 ± 10 to 9 13 mmHg and MCFP fell. Systemic vascular resistance did not change. Cardiac function was markedly depressed, and the heart rate increased from 143 ± 13 to 203 ± 30 beats x min⁻¹. L-NAME restored BP in both groups but also increased RVR and depressed cardiac function.

Changes in vascular tone during endotoxemia are dependent on volume status. The increased cardiac output in volume-treated septic animals occurred because of an increase in stressed volume due to the volume given in combination with a dilated vasculature. L-NAME restored arterial tone but decreased CO because of a rise in RVR and decrease in cardiac function.     

Treatment with N-acetylcysteine during acute respiratory distress syndrome: A randomized, double-blind, placebo-controlled clinical study

Intravenous N-acetylcysteine (NAC) has been reported to improve systemic oxygenation and reduce the need for ventilatory support in patients with an acute lung injury. In the more serious form, namely established adult respiratory distress syndrome (ARDS) (Pao₂/Fio₂ ≤ 200 mm Hg), we tested the hypothesis that treatment with intravenous NAC may be beneficial.

Respiratory dysfunction was graded daily according to the need for mechanical ventilation and Fio₂ and to the evolution of the lung injury score (LIS) and the Pao₂/Fi0₂ ratio in 42 patients with established ARDS receiving either NAC 190 mg/kg/day or placebo as a continuous intravenous infusion over the first 3 days of their clinical course.

NAC and placebo groups (22 and 20 patients, respectively) were comparable for demographic characteristics, ARDS categories, severity of illness (simplified acute physiology score [SAPS II]) LIS and Pao₂/Fio₂ ratio. Mortality rate was 32% for the NAC and 25% for the placebo group (difference not significant). At admission (day 1), 91% of patients in the NAC and 95% in the placebo group required ventilatory support; at days 2, 3, 5, and 7 after admission, the percentage of patients receiving ventilatory support was not significantly reduced for both groups in comparison with day 1. Moreover, there were no differences between the two groups at the same observation days. In both groups, the Fio₂ was significantly lower and the Pao₂/Fio₂ ratio was significantly higher than the initial values during the evolution (Fio₂ at day 3, P < .01 for NAC and P < .05 for placebo; Pao₂/Fio₂ at day 3: P < .01 for NAC and P < .02 for placebo), but this improvement was similar for both groups and, moreover, the between-group comparison was never significantly different at the various collection days. The LIS decreased significantly in NAC group between days 1 and 3 (2.23 ± 0.62 v 1.76 ± 0.17; P < .05), whereas no changes were observed in the placebo group; at day 5, there was a significant difference between the two groups (1.53 ± 0.21 for the NAC v 2.15 ± 0.19 for the placebo group; P < .05). In the prevalent sepsis category (10 patients in the NAC and 9 in the placebo group), the mortality rate, the need of ventilatory support, the intensive care unit stay, and the Pao₂/Fio₂ evolution did not differ significantly in both subgroups.

In this relatively small group of patients presenting with an established ARDS subsequent to a variety of underlying diseases, intravenous NAC treatment during 72 hours neither improved systemic oxygenation nor reduced the need for ventilatory support oxygenation nor reduced the need for ventilatory support.     

Sepsis: Evidence-based pathogenesis and treatment

Sepsis can develop during the body’s response to a critical illness leading to multiple organ failure, irreversible shock, and death. Sepsis has been vexing health care providers for centuries due to its insidious onset, generalized metabolic dysfunction, and lack of specific therapy. A common factor underlying sepsis is the characteristic hypermetabolic response as the body ramps up every physiological system in its fight against the underlying critical illness. A hypermetabolic response requires supraphysiological amounts of energy, which is mostly supplied via oxidative phosphorylation generated ATP. A by-product of oxidative phosphorylation is hydrogen peroxide (H₂O₂), a toxic, membrane-permeable oxidizing agent that is produced in far greater amounts during a hypermetabolic state. Continued production of mitochondrial H₂O₂ can overwhelm cellular reductive (antioxidant) capacity leading to a build-up within cells and eventual diffusion into the bloodstream. H₂O₂ is a metabolic poison that can inhibit enzyme systems leading to organ failure, microangiopathic dysfunction, and irreversible septic shock. The toxic effects of H₂O₂ mirror the clinical and laboratory abnormalities observed in sepsis, and toxic levels of blood H₂O₂ have been reported in patients with septic shock. This review provides evidence to support a causal role for H₂O₂ in the pathogenesis of sepsis, and an evidence-based therapeutic intervention to reduce H₂O₂ levels in the body and restore redox homeostasis, which is necessary for normal organ function and vascular responsiveness.     

感染性休克患者外周血T淋巴细胞凋亡和影响因素分析

目的观察感染性休克患者的外周血T淋巴细胞的凋亡情况,并对可能诱导T淋巴细胞凋亡的原因进行探讨。方法采集南京市第一医院ICU自2006年1月至2009年1月收治的32例感染性休克患者的外周血,用Annexin-V法和流式细胞仪测定其中的T淋巴细胞的凋亡情况,同时用酶联免疫法（ELISA）测定血浆中肿瘤坏死因子α（TNF-α）、白细胞介素10（IL-10）、白细胞介素1β（IL-1β）的浓度,用化学发光法检测血浆中的游离皮质醇浓度,将上述的结果和脓毒血症病患者及健康对照（n=22）相比。结果在初始状态下,外周血T淋巴细胞CD4＋亚群在健康对照组、脓毒血症组及感染性休克组分别为（4.41±1.45）%、（7.87±3.82）%及（11.01±4.52）%,感染性休克患者的外周血T淋巴细胞CD4＋亚群的凋亡比例高于脓毒血症患者（P〈0.05）,脓毒血症患者高于健康对照组（P〈0.05）;而初始状态下健康对照组、脓毒血症组及感染性休克组患者外周血T淋巴细胞CD8＋亚群的凋亡为（9.62±8.32）%、（13.09±15.84）%及（11.33±19.62）%,3组比较差异无统计学意义（P〉0.05）。在基础状态下TNF-α的浓度在健康对照组,脓毒血症组及感染性休克组中分别为（16.44±9.55）ng/L、（29.58±13.6）ng/L及（47.99±25.63）ng/L,感染性休克组TNF-α的浓度高于脓毒血症组（P〈0.05）,脓毒血症组高于健康对照组（P〈0.05）,持续72小时;IL-10的浓度在健康对照组,脓毒血症组及感染性休克组中分别为（6.38±7.5）ng/L、（9.67±4.88）ng/L及（15.01±5.36）ng/L,感染性休克组中的IL-10的浓度高于脓毒血症组（P〈0.05）,脓毒血症组高于健康对照组（P〈0.05）,持续72小时;游离皮质醇的浓度在健康对照组,脓毒血症组及感染性休克组中分别为（0.45±0.42）μmol/L、（0.87±0.49）μmol/L及（1.39±0.84）μmol/L,感染性休克组中的游离皮质醇浓度高于脓毒血症组（P〈0.05）,脓毒血症组高于健康对照组（P〈0.05）,持续72小时;IL-1β在健康对照组、脓毒血症组及感染性休克组中分别为（13.12±5.07）ng/L、（25.21±14.76）ng/L及（22.94±22.01）ng/L,感染性休克组和脓毒血症组的浓度高于健康对照组（P〈0.05）,但是感染性休克组和脓毒血症组的浓度差异无统计学意义（P〉0.05）。结论感染性休克患者的外周血T淋巴细胞中CD4＋亚群可发生明显的凋亡,TNF-α、IL-10及皮质醇可能参与了诱导CD4＋亚群的凋亡。     

Nitric oxide metabolism in canine sepsis: relation to regional blood flow

To investigate the role of nitric oxide (NO) in early endotoxemia on the systemic and regional blood flow by measuring the plasma nitrite/nitrate (NOx) and blood nitrosyl-hemoglobin (NO-Hb) levels.

This was a prospective, controlled, experimental study conducted in an animal research laboratory on 15 male mongrel dogs. Escherichia coli endotoxin (1 mg/kg) was injected intravenously.

Hepatic, renal, and iliac blood flow and cardiac output (CO) were measured before and 15, 30, 45, 90 and 180 minutes after injection of Escherichia coli endotoxin (1 mg/kg) (n = 6). NOx efflux from the organs was calculated by measuring plasma NOx levels. The arterial blood levels of NO-Hb were also measured (n = 4). As control studies, blood samples from dogs (n = 5) without exposure to endotoxin were assayed at 180 minutes for NOx and NO-Hb. Following endotoxin injection, mean arterial pressure decreased and reached its lowest value at 90 minutes (baseline vs. 90 minutes: 119.1 ± 5.8 vs. 82.5 ± 16.7 mm Hg, P < .0001). Hepatic artery bloodflow increased significantly (baseline vs. 180 minutes: 23.6 ± 12.0 vs. 170.0 ± 68.4 mL/min, P < .0001). There were no significant changes in plasma levels of NOx, uptake or release of NOx across the measured vascular beds, NO-Hb levels at anytime point. In the portal system, the portal vein flow correlated with NOx release (R = 0.69, P < .0001).

In the early phase of endotoxemia in the dog, the significant reduction in systemic vascular resistance and hepatic arterial resistance are not associated with any measurable NOx release in the systemic circulation or the liver.     

Measurement of gastric mucosal carbon dioxide tension by saline and air tonometry

This study compares the balloon air tonometry method of measuring gastric mucosal CO₂ to standard saline tonometry. Also, this study investigates the effect of histamine-2 receptor blockade on the precision of tonometric measures of gastric mucosal Pco₂ (P_tco₂).

We obtained hourly measurements of P_tco₂ from two gastric tonometers inserted orally in 19 healthy volunteers. One tonometer measured P_tco₂ by the intermittent saline method, whereas the other measured P_tco₂ using a newer continuous air method. Subjects received intravenous 5% dextrose during the first 6 hours of the experiment followed by a continuous infusion of a solution of ranitidine in 5% dextrose for another 6 hours. The ranitidine infusion was titrated to maintain gastric fluid pH ≥ 4.

Comparison of air to saline tonometry yielded a bias of −1.3 mm Hg with a limit of agreement of 6.6 mm Hg under optimal conditions of optimal gastric fluid pH (gastric fluid pH ≥ 5.0). Measures of P_tco₂ were lower with ranitidine for either group, 45.3 ± 1.3 mm Hg versus 39.7 ± 0.5 mm Hg for saline (P < .01) and 45.9 ± 1.0 versus 41.3 ± 0.5 for air (P < .01). The mean Pco₂ gap (P_tco₂ - P_arterialco₂) at gastric fluid pH ≥ 5.0 was 1.4 mm Hg, with a standard deviation of 2.7 mm Hg. A span of three standard deviations yields a normal limit for Pco₂ gap of 9.5 mm Hg.

Measures of P_tco₂ with the air tonometer method are similar to those obtained with saline tonometry. The reliability of P_tco₂ measurements with either method improved with the use of ranitidine to maintain gastric fluid pH ≥5.     

Blood histamine concentrations are not elevated in humans with septic shock

Histamine has been suggested as an important mediator of the cardiovascular abnormalities during septic shock. To determine if blood histamine levels were increased during human sepsis and septic shock, plasma histamine was measured using a very sensitive radioenzyme assay employing histamine N-methyltransferase (HNMT) in the following patient groups: normal controls (n = 76), nonseptic critically ill (n = 12), nonseptic shock (n = 2), sepsis without shock (n = 28), and septic shock (n = 41). Using this enzyme binding assay, all these groups had similar, normal plasma histamine concentrations, except those patients with septic shock whose mean histamine measurements were significantly reduced (p less than .002). This decrease was found to be due to an artifact of the assay: plasma contained a circulating inhibitor that falsely lowered the measured histamine level. Fractionation of septic shock plasma using molecular exclusion membranes and gel filtration revealed a 5000 MW inhibitory factor. After removal of this inhibitor from plasma, septic shock plasma histamine levels were normal. Thus, septic shock patients may have a circulating inhibitor of the HNMT enzyme, but plasma histamine concentrations are normal. Histaminemia is unlikely to play an important role in the pathogenesis of septic shock in humans.     

Visfatin levels in patients with severe pneumonia

BACKGROUND: As a cytokine highly expressed in internal organs, visfatin could be used as a biomarker of systemic inflammation response for chronic obstructive pulmonary diseases, but few studies have reported the use of visfatin in severe pneumonia. The present study was undertaken to determine the plasma levels of visfatin in patients with severe pneumonia.METHODS: A total of 70 patients, including 40 patients with severe pneumonia (group A) and 30 patients with non severe pneumonia (group B) who had been admitted to the ICU from June 2009 to June 2010, were enrolled in this prospective study. And another 30 healthy physical examinees served as healthy controls (group C). Patients were excluded if they suffered from severe diseases of the heart, brain and kidney, cancers, autoimmune diseases, or received special treatment in the latest month. The plasma levels of visfatin, IL-6, IL-8 and TNF-α were measured by ELISA, while the level of CRP was determined by immuneturbidimetry, and the routine blood test was performed. Blood gas analysis and Acute Physiology and Chronic Health Evaluation II (APACHE II) were performed in patients with pneumonia. Comparisons between the groups were conducted by Student's t test, ANOVA or nonparametric test. Correlation analysis was carried out by Pearson's correlation test or Spearman's rank-order correlation test.RESULTS: The plasma level of visfatin in group A was significantly higher than that in groups B and C (P<0.001), and the level of visfatin in group B was significantly higher than that in group C (P<0.001). The plasma level of visfatin was positively correlated with CRP, TNF-α, APACHE II and PMN% in patients with severe pneumonia (r_ho=0.653, r=0.554, r=0.558, r=0.484, respectively, P<0.05 for all), while it was negatively correlated with PaO₂ and PaO₂/FiO₂ (r_ho=-0.422, r=-0.543, respectively, P<0.05 for all).CONCLUSION: Visfatin may be involved in the systematic inflammation response in patients with severe pneumonia as a pro-inflammatory cytokine, and it is valuable in assessing the severity of pneumonia..     

Clinical trial of an ex vivo arterial blood gas monitor

The purpose of this study was to test the performance of a patient attached, on demand ex vivo arterial blood gas (ABG) monitor, and to compare the frequency of ABG analysis using the monitor, where the monitor was operated by intensive care unit (ICU) staff on shock trauma and neurosurgical intensive care patients for s6 days, with standard clinical laboratory analysis.

The ABG monitor (SensiCath; Optical Sensors Inc., Minneapolis, MN) incorporates fiber optic pH, P_co2, P_o2 and thermistor temperature sensors in a 0.3-mL sensor chamber that attaches in line with the patient's arterial pressure tubing and connects via a fiberoptic cable to a bedside instrument. The monitor and standard clinical laboratory performance were compared following an institutionally approved protocol. Adult ICU patients (n = 30) were studied for whom an arterial cannula was required, the expected ICU stay was>72 hours, ≥2 ABG analyses/day were anticipated, and informed consent had been obtained. Paired comparison ABG analyses and quality assurance checks were performed daily. The frequency of ABG analyses in this study, for which monitor values were used for clinical decision making, was compared with the frequency previously reported for the same ICUs, for which the monitor and laboratory results were compared but only the latter were used for clinical decision making.

Five hundred ABG analyses, 436 over the first 72 hours, were obtained using the monitor for patient management over 3,248 patient hours (85 ± 47 hours/ patient). Monitor-laboratory comparison ABG analyses (n = 258) indicated stable performance over 6 days: For pH, the range of laboratory measurements was 7.200 to 7.540, accuracy (mean difference between monitor and laboratory measurement) was +0.013, and precision (standard deviation of difference between monitor and laboratory measurements) was ±0.031. For Pco₂, range: 18 to 78.5, accuracy: −0.8, precision: ±3.4 mm Hg. For P02, range: 41.0 to 344.0, accuracy: +2.3, precision: ±12.8 mm Hg. The frequency of ABG analyses obtained using the monitor (ie, 15.0 ± 11.6 ABGs/patient/72 hours) was significantly greater than that using the clinical laboratory (ie, 8.8 ± 4.2 ABGs/patient/72 hours) (P = .01).

The ABG monitor provides performance comparable to standard clinical laboratory analysis for ≤6 days (≤144 hours), consistent with ICU arterial cannula changeout schedules. More frequent ABG analyses are obtained by critical care practitioners using the monitor compared with the clinical laboratory system, suggesting that clinical decision making based on ABG data may be limited by the frequency of ABG analysis.     

Estimation of cholesterol sulphate in blood plasma and in erythrocyte membranes from individuals with Down''s syndrome or diabetes mellitus type I

Objectives: Plasma and erythrocyte membrane cholesterol sulphate (CS) were measured in patients suffering from diabetes and Down's syndrome.

Design and Methods: The procedure for separation and determination of CS comprised HPTLC (high-performance thin-layer chromatography) and densitometry.

Results: The mean plasma and RBC membranes CS concentrations (±SD) of the control group (n = 16) was 188 ± 47 μg/dL and 343 ± 57 μg/10¹² RBC, respectively. In 15 patients with diabetes and 12 Down's syndrome patients substantially higher CS levels were found (diabetes: plasma-348 ± 60 μg/dL; RBC membranes-646 ± 113 μg/10¹² RBC; Down's syndrome: plasma-245 ± 54 μg/dL; RBC membranes 427 ± 74 μg/10¹² RBC). Analysis of variance and multiple comparison (Newman-Keuls test) show statistically significant differences between all samples both for erythrocytes, F(2,41) = 52.24, p < 0.05, and plasma, F(2,41) = 34.92, p < 0.05.

Conclusions: It is postulated that differences in CS levels may contribute to changes of erythrocyte properties in these pathological states.     

Evaluation of the etest for antimicrobial spectrum and potency determinations of anaerobes associated with bacterial vaginosis and peritonitis

One hundred ninety-seven anaerobic organisms (24 Gardnerella vaginalis, 16 Mobiluncus spp., 19 Peptostreptococcus spp., 20 Lactobacillus spp., 20 Prevotella bivia/disiens, 81 Bacteroides fragilis group, 12 Clostridium spp., and five Fusobacterium spp.) were processed by the Etest (AB Biodisk, Solna, Sweden) and a reference (Brucella blood agar) method against 10 antimicrobial agents. For the bacterial vaginosis-associated pathogens, the Etest was more reproducible and correlated acceptably with the reference agar test: within ±1 log₂ dilution for 74.4% of Mobiluncus spp. to 96.0% for Peptostreptococcus spp. (all organisms, 83.4%). The quantitative correlation ±2 log₂ dilution steps between test results was 94.3%. Results with B. fragilis group strains demonstrated 97.3% correlation (±2 log₂ dilution) with a trend toward slightly lower Etest minimum inhibitory concentrations for ampicillin-sulbactam, cefotaxime, imipenem, and clindamycin. The absolute qualitative interpretive agreement between Etest and the reference agar dilution method results was 94.4%, with only a 0.4% false-susceptible error rate. The Etest appears to be a very practical, quantitatively accurate, alternative procedure for clinical microbiology laboratories routinely testing the susceptibilities of anaerobes and, by these presented data, organisms associated with female tract infections.     

Plasma antioxidant status in septic critically ill patients: a decrease over time

Severe septic states in humans are responsible for intense intravascular oxidative stress, which induces numerous adaptive mechanisms. We determined time sequence changes in total plasma antioxidant capacity (TAC) and major plasma antioxidant concentrations, which have not been fully explained in septic conditions. A cohort of 56 consecutive septic patients (septic shock n = 37, severe sepsis n = 19) and six healthy volunteers. We compared TAC and antioxidant levels in patients with one of two degrees of septic states, at the onset of illness, to those of healthy volunteers. Thereafter, over a 10-day follow-up, we observed daily the time sequence changes of the two septic populations in terms of TAC and antioxidants. At the onset, there was no difference between the three groups in terms of TAC values (healthy subjects 2.18 +/- 0.04; severe sepsis 2.03 +/- 0.07; septic shock 2.09 +/- 0.09), then an equivalent time decline was observed in the two septic populations whatever the severity. TAC was statistically linked to uric acid, proteins in particular albumin and bilirubin (multivariate analysis), but no correlation was found with any vitamin (A, C and E). A sharp and persistent decrease in vitamin C concentrations was underlined. TAC, unaffected at first, deteriorated over time whatever the severity of the infection in these critically ill patients. TAC, unable to distinguish severe sepsis and septic shock, is unlikely to be a particularly useful outcome measure.     

Effects of high-volume hemofiltration on alveolar-arterial oxygen exchange in patients with refractory septic shock

BACKGROUND: High-volume hemofiltration (HVHF) is technically possible in severe acute pancreatitis (SAP) patients complicated with multiple organ dysfunction syndrome (MODS). Continuous HVHF is expected to become a beneficial adjunct therapy for SAP complicated with MODS. In this study, we aimed to explore the effects of fluid resuscitation and HVHF on alveolar- arterial oxygen exchange, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with refractory septic shock.METHODS: A total of 89 refractory septic shock patients, who were admitted to ICU, the Provincial Hospital affiliated to Shandong University from August 2006 to December 2009, were enrolled in this retrospective study. The patients were randomly divided into two groups: fluid resuscitation (group A, n=41), and fluid resuscitation plus high-volume hemofiltration (group B, n=48). The levels of O₂ content of central venous blood (C_cvO₂), arterial oxygen content (C_aO₂), alveolar-arterial oxygen pressure difference P_(A-a)DO₂, ratio of arterial oxygen pressure/alveolar oxygen pressure (P_aO₂/P_AO₂), respiratory index (RI) and oxygenation index (OI) were determined. The oxygen exchange levels of the two groups were examined based on the arterial blood gas analysis at different times (0, 24, 72 hours and 7 days of treatment) in the two groups. The APACHE II score was calculated before and after 7-day treatment in the two groups.RESULTS: The levels of C_cvO₂, C_aO₂ on day 7 in group A were significantly lower than those in group B (C_cvO₂: 0.60±0.24 vs. 0.72±0.28, P<0.05; CaO₂: 0.84±0.43 vs. 0.94±0.46, P<0.05). The level of oxygen extraction rate (O₂ER) in group A on the 7th day was significantly higher than that in group B ( 28.7±2.4 vs. 21.7±3.4, P<0.01). The levels of P_(A-a)DO₂ and RI in group B on the 7th day were significantly lower than those in group A. The levels of P_aO₂/P_AO₂ and OI in group B on 7th day were significantly higher than those in group A (P<0.05 or P<0.01). The APACHE II score in the two groups reduced gradually after 7-day treatment, and the APACHE II score on the 7th day in group B was significantly lower than that in group A (8.2±3.8 vs. 17.2±6.8, P<0.01).CONCLUSION: HVHF combined with fluid resuscitation can improve alveolar- arterial-oxygen exchange, decrease the APACHE II score in patients with refractory septic shock, and thus it increases the survival rate of patients.     

Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats

BACKGROUND: Dexmedetomidine has already been used in septic patients as a new sedative agent, few studies have examined its effects on immunomodulation. Therefore, the authors have designed a controlled experimental study to characterize the immunomodulation effects of dexmedetomidine in the cecal ligation and puncture (CLP) model in rats.METHODS: After CLP, 48 Wistar rats were randomly allocated into four groups: (1) CLP group; (2) small-dose treatment group (2.5 μg·kg ^-1·h^-1); (3) medium-dose treatment group (5.0 μg·kg ^-1· h^-1); and (4) large-dose treatment group (10.0 μg·kg ^-1·h^-1). HLA-DR and plasma cytokine (IL-4, IL-6, IL-10 and TNF-α) levels were measured, and the mean arterial blood pressure (MAP), heart rate (HR), arterial blood gases, lactate concentrations and mortality were also documented. RESULTS: The HLA-DR level, inflammatory mediator levels, MAP and HR had no obvious changes among Dexmedetomidine treatment groups (DEX groups). Compared with the CLP group, the DEX groups exhibited decreased HLA-DR levels (P_group=0.0202) and increased IL-6 production, which was increased at 3 h (P= 0.0113) and was then attenuated at 5 h; additionally, the DEX groups exhibited decreased HR (P<0.001) while maintaining MAP (P_group=0.1238), and remarkably improving lactate (P<0.0001). All of these factors led to a significant decrease in the mortality, with observed rates of 91.7%, 66.7%, 25% and 18% for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively. CONCLUSION: Dexmedetomidine treatment in the setting of a CLP sepsis rat model has partially induced immunomodulation that was initiated within 5 h, causing a decreased HR while maintaining MAP, remarkably improving metabolic acidosis and improving mortality dose-dependently.