Protective effect of pentoxifylline plus thalidomide against septic shock in mice

Mortality caused by septic shock in experimental animals is reduced by thalidomide, an inhibitor of tumour necrosis factor alpha. Another drug that could act on the pathophysiological mechanisms of septic shock is pentoxifylline, an inhibitor of platelet aggregation that increases the flexibility of the erythrocyte membrane and has fibrinolytic activity. We studied the effect of pentoxifylline alone and combined with thalidomide in septic shock; 97 NIH mice were injected with lipopolysaccharides of Salmonella abortus equi and D galactosamine. Animals were separated in 4 groups; group A (n = 20) was used as control, group B (n = 15) received thalidomide 50 mg/kg, group C (n = 20) received pentoxifylline 40 mg/kg, and group D (n = 15) received thalidomide plus pentoxifylline. Mortality was recorded every hour. Additionally, 5 animals from each group were sacrificed 8 h after the induction of septic shock for histological analysis of heart, lung, brain, kidney, small intestine, adrenal glands and liver. Microscopic findings were rated as absent, mild, moderate and severe damage. In control animals histological analysis showed intense haemorrhage and necrosis in all organs studied. When compared with controls, treatment with pentoxifylline plus thalidomide reduced mortality (P < 0.03). The tissue damage was less severe in animals from the groups that received pentoxifylline or pentoxifylline plus thalidomide (P < 0.05). Pentoxifylline seems to potentiate the beneficial effects of thalidomide, reducing mortality and attenuating the pathological changes produced by septic shock.     

Use of intravenous immunoglobulin therapy in the treatment of septic shock, in particular severe invasive group A streptococcal disease

Group A streptococcus (GAS) is a β-hemolytic bacterium often found in the throat and skin. The two most severe clinical manifestations of GAS are streptococcal toxic shock syndrome and necrotizing fasciitis. Intravenous immunoglobulin (IVIg) is a gamma globulin made from purified pooled plasma of thousands of donors, consisting mainly of IgG. We report the case of a 40-year-old man admitted after 2 days of vomiting and severe right-sided chest pain. He was hypotensive with a sinus tachycardia, pyrexial, and vasodilated. The only other positive finding was a swollen and erythematous chest wall. Muscle layer biopsies and blood cultures soon grew extensive GAS, and an initial diagnosis of necrotizing fasciitis was made. The clinical syndrome was of severe septic shock secondary to invasive GAS. The patient quickly deteriorated with a worsening metabolic acidosis. Despite maximal intensive care therapy including fluids, vasoactive agents, and also activated protein C, the patient continued to remain profoundly hypotensive. A decision was made to commence IVIg, with the aim of immunomodulation of the inflammatory cascade seen in sepsis. Over the next 24 hours the patient improved, was extubated 3 days later, and subsequently discharged from hospital after 2 weeks. Although the evidence for the use of IVIg in severe invasive GAS disease is limited, we feel that on reviewing the available literature its use in this case was justified. The limited worldwide supply and high costs, together with a limited evidence base, warrant restricting its use to cases in which conventional therapy has failed. The literature for use of intravenous immunoglobulin in invasive GAS infection will be reviewed in this article.     

Procalcitonin kinetics as a prognostic marker in severe sepsis/septic shock

Background and Aims:

To evaluate the prognostic value of change (fall) in serum procalcitonin level (PCT) in critically ill adults with severe sepsis/septic shock.

Methods:

This was a prospective observational study in a general purpose Intensive Care Unit of a teaching Institute. PCT was measured at admission (D0) and after 72–96 h (D4) by electrochemi-luminescence immunoassay (BRAHMS PCT kit) in adults (>18 years) admitted with severe sepsis or septic shock. Change in procalcitonin values from D0 to D4 was correlated with the primary outcome, that is, 28 days mortality. All results are reported as median (interquartile range).

Results:

A total of 171 (100 males) of 181 patients were included. The median age was 46 years (range 19–79). 137 patients were in septic shock and 34 in severe sepsis. The sequential organ failure assessment (SOFA) score in all patients was 11 (9–14).91 (53.2%) patients survived at 28 days (survivors). The baseline procalcitonin was similar in two groups (3.48 [1.04–15.85] vs. 5.27 [1.81–23.57] ng/ml in survivors and nonsurvivors [NS] respectively). The procalcitonin change was 1.58 (0.20–8.52) in survivors and 0.28 (–1.38–6.17) in NS (P = 0.01). The C-statistic of percentage change in procalcitonin from D0 to D4 to predict survival was 0.73 (95% confidence interval [CI]: 0.65–0.82) when compared to 0.78 (95% CI: 0.71–0.86) for change of SOFA score. For an absolute fall in procalcitonin of >1 ng/ml, a 70% fall predicted survival with 75% sensitivity and 64% specificity.

Conclusions:

In critically ill-patients with severe sepsis/septic shock, change (fall) in procalcitonin is associated with good outcome.     

Left atrial function for outcome prediction in severe sepsis and septic shock: An echocardiographic study

Left ventricular function and B-type natriuretic peptide (BNP) assessments are used to predict mortality in septic patients. Left atrial function has never been used to prognosticate outcome in septic patients.

Objectives:

To assess if deterioration of left atrial function in patients with severe sepsis and septic shock could predict mortality.

Methods:

We studied 30 patients with severe sepsis or septic shock with a mean age of 49.8±16.17. Echocardiographic parameters were measured on admission, Day 4, and Day 7, which comprised left ventricular ejection fraction (EF), and atrial function that is expressed as atrial ejection force (AEF). All patients were subjected to BNP assay as well. Multivariate analyses adjusted for APACHE II score was used for mortality prediction.

Results:

The underlying source for sepsis was lung in 10 patients (33%), blood in 7 patients (23.3%), abdomen in 7 patients (23.7%), and 3 patients (10%) had UTI as a cause of sepsis. Only one patient had CNS infection. In-hospital mortality was 23.3% (7 patients). Admission EF showed a significant difference between survivors and non survivors, 49.01±6.51 vs.. 56.44±6.93% (P<0.01). On the other hand, admission AEF showed insignificant changes between the same groups, 10.9±2.81 vs. 9.41±2.4 k/dynes P=0.21, while BNP was significantly higher in the non survivors, 1123±236.08 vs. 592.7±347.1 pg/ml (P<0.001). The predicatable variables for mortality was Acute Physiology and Chronic Health Evaluation II score, BNP, then EF.

Conclusion:

In septic patients, left atrial function unlike the ventricular function and BNP levels can not be used as an independent predictor of mortality.     

Serum lactate levels as the predictor of outcome in pediatric septic shock

Background and Aims:

An association of high lactate levels with mortality has been found in adult patients with septic shock. However, there is controversial literature regarding the same in children. The aim of this study was to find the correlation of serum lactate levels in pediatric septic shock with survival.

Settings and Design:

This was a prospective observational study at PICU of a tertiary care center of North India.

Materials and Methods:

A total of 30 children admitted to PICU with diagnosis of septic shock were included in the study. PRISM III score and demographic characteristics of all children were recorded. Serum lactate levels were measured in arterial blood at 0-3, 12, and 24 h of PICU admission. The outcome (survival or death) was correlated with serum lactate levels.

Results:

Septic shock was the most common (79.3%) type of shock and had 50% mortality. Initial as well as subsequent lactate levels were significantly higher in nonsurvivors. A lactate value of more than 45 mg/dl (5 mmol/l) at 0–3, 12, and 24 h of PICU admission had an odds ratio for death of 6.7, 12.5, and 8.6 (95% CI: 1.044–42.431, 1.850–84.442, 1.241–61.683) with a positive predictive value (PPV) of 38%, 71%, 64% and a negative predictive value (NPV) of 80%, 83%, and 83%, respectively.

Conclusions:

Nonsurvivors had higher blood lactate levels at admission as well as at 12 and 24 h. A lactate value of more than 45 mg/dl (5 mmol/l) was a good predictor of death.     

Inhibition of septic shock in mice by an oligopeptide from the beta-chain of human chorionic gonadotrophin hormone

Human chorionic gonadotrophin (hCG) is a heterodimeric placental glycoprotein hormone required in pregnancy. In human pregnancy urine and in commercial hCG preparations (c-hCG) it occurs in a variety of forms, including breakdown products. Several reports have suggested modulation of the immune system by intact hormone, but such effects of breakdown products have not been reported. In a related article (Hum Immunol 62:1315, 2001), it is reported that a 400-2000 Dalton (Da) fraction from c-hCG and from human pregnancy urine inhibits Th1-mediated diabetes in NOD mice. The active component(s) were called natural (immuno)modulatory pregnancy factor(s) (NMPF). This study reports that a single treatment with the same low molecular weight NMPF fraction up to 24-h after high dose lipopolysaccharide (LPS) injection inhibited septic shock in mice. This counteracting effect of NMPF paralleled the downregulation of the effects of LPS on the production of macrophage migration inhibitory factor (MIF) by spleen cells, on the plasma level of liver aminotransferase, and on the expression of several splenic lymphocyte and macrophage surface markers. Based on the primary structure of the beta-chain of hCG a synthetic hexapeptide Valine-Leucin-Proline-Alanine-Leucine-Proline (VLPALP) was designed, which demonstrated it to have the same protective effects as the 400-2000 Da NMPF fraction. These results indicate a new strategy for the treatment of septic shock and the potential of therapeutic use of this synthetic oligopeptide.     

Impact of positive fluid balance on mortality and length of stay in septic shock patients

Background:

Fluid management is important in critically patients. The aim of this study was to determine the relationship between fluid balance and adverse outcomes of septic shock.

Methods:

A retrospective study was conducted in the medical Intensive Care Unit (ICU) of a tertiary university hospital in Thailand, over a 7-year period.

Results:

A total of 1048 patients with an ICU mortality rate of 47% were enrolled. The median cumulative fluid intake at 24, 48, and 72 h from septic shock onset were 4.2, 7.7, and 10.5 L, respectively. Nonsurvivors had a significantly higher median cumulative fluid intake at 24, 48, and 72 h (4.6 vs. 3.9 L, 8.2 vs. 7.1 L, and 11.4 vs. 9.9 L, respectively, P < 0.001 for all). Nonsurvivors also had a significantly higher cumulative and mean fluid balance within 72 h (5.4 vs. 4.4 L and 2.8 vs. 1.6 L, P < 0.001 for both). In multivariate logistic regression analysis, mean fluid balance quartile within 72 h, was independently associated with an increase in ICU and hospital mortality. Quartile 3 and 4 have statistically significant increases in mortality compared with quartile 1 (odds ratio [95% confidence interval] 3.04 [1.9–4.48] and 4.16 [2.49–6.95] for ICU mortality and 2.75 [1.74–4.36] and 3.16 [1.87–5.35] for hospital mortality, respectively, P < 0.001 for all). In addition, the higher amount of mean fluid balance was associated with prolonged ICU stays.

Conclusions:

Positive fluid balance over 3 days is associated with increased ICU and hospital mortality along with prolonged ICU stays in septic shock patients.     

Nitrosonisoldipine is a selective inhibitor of inflammatory caspases and protects against pyroptosis and related septic shock

Pyroptosis is a type of acute cell death that mainly occurs in immune cells. It is characterized with robust release of inflammatory cytokines and has emerged to play a critical role in the pathogenesis of sepsis-associated immune disorders. In this study, we screened for pyroptotic inhibitors with the ultimate goal to benefit sepsis treatments. Accidentally, we identified that nitrosonisoldipine (NTS), a photodegradation product of calcium channel inhibitor nisoldipine, inhibits noncanonical pyroptosis. Using murine immortalized BM-derived macrophage and human THP-1 cell line, we further discovered that NTS not only inhibits noncanonical pyroptosis mediated by caspase-11 or caspase-4 but also canonical pyroptosis mediated by caspase-1. Mechanistically, NTS directly inhibits the enzyme activities of these inflammatory caspases, and these inhibitory effects persist despite extensive washout of the drug. By contrast, apoptosis mediated by caspase-3/-7 was not affected by NTS. Mice pretreated with NTS intraperitoneally displayed improved survival rate and extended survival time in LPS- and polymicrobe-induced septic models, respectively. In conclusion, NTS is a selective inhibitor of inflammatory caspases that blocks both the noncanonical and canonical pyroptotic pathways. It is safe for intraperitoneal administration and might be used as a prototype to develop drugs for sepsis treatments.     

Accuracy of a real-time continuous glucose monitoring system in children with septic shock: A pilot study

Aims:

The aim of this prospective, observational study was to determine the accuracy of a real-time continuous glucose monitoring system (CGMS) in children with septic shock.

Subjects and Methods:

Children aged 30 days to 18 years admitted to the Pediatric Intensive Care Unit with septic shock were included. A real-time CGMS sensor was used to obtain interstitial glucose readings. CGMS readings were compared statistically with simultaneous laboratory blood glucose (BG).

Results:

Nineteen children were included, and 235 pairs of BG-CGMS readings were obtained. BG and CGMS had a correlation coefficient of 0.61 (P < 0.001) and a median relative absolute difference of 17.29%. On Clarke''s error grid analysis, 222 (94.5%) readings were in the clinically acceptable zones (A and B). When BG was < 70, 70–180, and > 180 mg/dL, 44%, 100%, and 76.9% readings were in zones A and B, respectively (P < 0.001). The accuracy of CGMS was not affected by the presence of edema, acidosis, vasopressors, steroids, or renal replacement therapy. On receiver operating characteristics curve analysis, a CGMS reading <97 mg/dL predicted hypoglycemia (sensitivity 85.2%, specificity 75%, area under the curve [AUC] =0.85). A reading > 141 mg/dL predicted hyperglycemia (sensitivity 84.6%, specificity 89.6%, AUC = 0.87).

Conclusion:

CGMS provides a fairly, accurate estimate of BG in children with septic shock. It is unaffected by a variety of clinical variables. The accuracy over extremes of blood sugar may be a concern. We recommend larger studies to evaluate its use for the early detection of hypoglycemia and hyperglycemia.     

Prevalence of occult adrenal insufficiency and the prognostic value of a short corticotropin stimulation test in patients with septic shock

Background:

Corticosteroid insufficiency in acute illness can be difficult to discern clinically. Occult adrenal insufficiency (i.e., Δmax ≤9 μg/dL) after corticotropin may be associated with a high mortality rate.

Objective:

To assess the prevalence of occult adrenal insufficiency and the prognostic value of short corticotropin stimulation test in patients with septic shock.

Materials and Methods:

A total of 30 consecutive patients admitted in the adult intensive care unit of the Sheri Kashmir Institute of Medical Sciences who met the clinical criteria for septic shock were prospectively enrolled in the study. A low dose (1 μg) short corticotropin stimulation test was performed; blood samples were taken before the injection (T0) and 30 (T30) and 60 (T60) minutes afterward.

Results:

The prevalence of occult adrenal insufficiency was 57%. The 28-day mortality rate was 60% and the median time to death was 12 days. The following seven variables remained independently associated with death: organ system failure scores, simplified acute physiology score II score, mean arterial pressure, low platelet count, PaO₂:FIO₂, random baseline cortisol (T0) >34 μg/dL, and maximum variation after test (Δmax) of ≤9 μg/dL. Three different mortality patterns were observed: (I) low (T0 ≤34 μg/dL and Δmax >9 μg/dL; a 28-day mortality rate of 33%),(II) intermediate (T0 >34 μg/dL and Δmax >9 μg/dL or T0 ≤34 μg/dL and Δmax ≤9 μg/dL; a 28-day mortality rate of 71%), and (III) high (T0 >34 μg/dL and Δmax ≤9 μg/dL; a 28-day mortality rate of 82%).

Conclusion:

A short corticotropin test using low-dose corticotropin (1 μg) has a good prognostic value. High basal cortisol and a low increase in cortisol on corticotropin stimulation test are predictors of a poor outcome in patients with septic shock.     

Role of steroids in septic shock: Assessment of knowledge, attitudes and practices among intensivists practising in Hyderabad

Context:

Use of steroids in septic shock is an issue of contention, more so with two major trials reporting conflicting results.

Aims:

To assess the current knowledge, attitudes and practices (KAP) related to the role of steroids in septic shock among intensivists practising in Hyderabad.

Setting, Design, Materials and Methods:

Questionnaires containing 10 questions pertaining to the role of steroids in septic shock, were distributed to 76 intensivists during the monthly critical care meeting.

Results:

A great majority of intensivists (82%) agreed that the role of steroids is restricted to septic shock not responding to vasopressors. There was no clear consensus regarding the role of corticotropin stimulation test or the timing of total cortisol level testing, if it has to be performed. Hydrocortisone was clearly the choice of steroid for most intensivists and intravenous bolus injection being the preferred route of administration. There was no agreement regarding the dose of steroids, the role of fludrocortisone and whether steroids should be tapered. Most of the respondents did not extend the steroid therapy beyond seven days and the most common side effect reported was hyperglycemia.

Conclusion:

There is a lot of ambiguity in the knowledge, attitudes or practices regarding role of steroids in septic shock among intensivists in Hyderabad. Uniform policies and protocols need to be devised at institutional level, with multispecialty inputs, and doctors need to be familiarized accordingly.     

Differential effects of prophylactic,concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice

Mice injected with endotoxin develop endotoxaemia and endotoxin-induced death, accompanied by the oxidative burst and overproduction of inflammatory mediators. Lactoferrin, an iron binding protein, provides a natural feedback mechanism to control the development of such metabolic imbalance and protects against deleterious effects of endotoxin. We investigated the effects of intraperitoneal administration of human lactoferrin on lipopolysaccharide (LPS)-induced release of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 10 (IL-10) and nitric oxide (NO) in vivo. Lactoferrin was administered as a prophylactic, concurrent or therapeutic event relative to endotoxic shock by intravenous injection of LPS. Inflammatory mediators were measured in serum at 2, 6 and 18 h post-shock induction. Administration of lactoferrin 1 h before LPS resulted in a rather uniform inhibition of all mediators; TNF by 82%, IL-6 by 43%, IL-10 by 47% at 2 h following LPS injection,and reduction in NO (80%) at 6 h post-shock. Prophylactic administration of lactoferrin at 18 h prior to LPS injection resulted in similar decreases in TNF-alpha (95%) and in NO (62%), but no statistical reduction in IL-6 or IL-10. Similarly, when lactoferrin was administered as a therapeutic post-induction of endotoxic shock, significant reductions were apparent in TNF-alpha and NO in serum, but no significant effect was seen on IL-6 and IL-10. These results suggest that the mechanism of action for lactoferrin contains a component for differential regulation of cellular immune responses during in vivo models of sepsis.     

Protective effect of taraxasterol against LPS-induced endotoxic shock by modulating inflammatory responses in mice

Taraxasterol, a pentacyclic-triterpene, was isolated from the Chinese medicinal herb Taraxacum officinale. In the present study, we investigated the protective effect of taraxasterol on murine model of endotoxic shock and the mechanism of its action. Mice were treated with 2.5, 5 and 10?mg/kg of taraxasterol prior to a lethal dose of lipopolysaccharide (LPS) challenge. Survival of mice was monitored twice a day for 7 days. To further understand the mechanism, the serum levels of inflammatory cytokine tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6) and mediator nitric oxide (NO), prostaglandin E₂ (PGE₂) as well as histology of lungs were examined. The results showed that taraxasterol significantly improved mouse survival and attenuated tissue injury of the lungs in LPS-induced endotoxemic mice. Further studies revealed that taraxasterol significantly reduced TNF-α, IFN-γ, IL-1β, IL-6, NO and PGE₂ levels in sera from mice with endotoxic shock. These results indicate that taraxasterol has a protective effect on murine endotoxic shock induced by LPS through modulating inflammatory cytokine and mediator secretion. This finding might provide a new strategy for the treatment of endotoxic shock and associated inflammation.     

Selection of acute blood purification therapy according to severity score and blood lactic acid value in patients with septic shock

Aim:

As an alternative method for acute blood purification therapy, continuous venovenous hemodiafiltration (CVVHDF) has been reported as an effective clinical treatment for critically ill patients, but the optimal column for performing CVVHDF remains controversial.

Patients and Methods:

We used direct hemoperfusion using a polymyxin B-immobilized fiber column (DHP-PMX) to treat 88 patients with septic shock. To determine the optimal acute blood purification therapy, we subsequently divided the patients into three groups: the first group underwent CVVHDF using a polymethylmethacrylate membrane hemofilter (PMMA) after undergoing DHP-PMX (28 cases), the second group underwent CVVHDF using a polyacrylonitrile membrane hemofilter (PAN) after undergoing DHP-PMX (26 cases), and the third group did not undergo CVVHDF after undergoing DHP-PMX (34 cases).

Results:

The overall survival rate was 54.5%, and patient outcome was significantly related to the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the sepsis-related organ failure assessment (SOFA) score, and the blood lactic acid value before treatment (all P<0.0001). Only the PMMA-CVVHDF group showed a better outcome (survival rate of 78.6%) compared with the other groups (P = 0.0190). In addition, only the PMMA-CVVHDF group showed a significant improvement in the blood lactic acid level on day 3 (P = 0.0011).

Conclusion:

Our study suggests that the PMX column might be effective during the early phase of septic shock, before a high level of lactic acid is present. Furthermore, a PMMA column might be the most useful column for performing CVVHDF after DHP-PMX treatment, as suggested by the blood lactic acid value.     

Safety and efficacy of polymyxin B in multidrug resistant Gram-negative severe sepsis and septic shock

Background and Aims:

The emergence of multidrug resistant strains of Gram-negative bacteria, especially the lactose nonfermenters like Pseudomonas and Acinetobacter, in the intensive care units have prompted renewed worldwide interest in the polymyxins. However, perceived nephrotoxicity has been a major vexation limiting their early and regular use in severe sepsis. This study was conducted to assess the safety and efficacy of polymyxin B in patients with severe sepsis and septic shock.

Materials and Methods:

Forty-five patients with sepsis admitted in our medical-surgical intensive care units were identified from pharmacy records to have received polymyxin B. We retrospectively reviewed the clinical and microbiologic outcomes as well as occurrence of renal failure temporally related to the use of intravenous polymyxin B.

Results:

polymyxin B was used in severe sepsis and septic shock with the isolated organism being resistant to other available antimicrobials or clinical deterioration despite carbapenem use. Overall mortality was 52% and among patients who received at least eight days of intravenous polymyxin B, 67% patients with initial septic shock and 62% with severe sepsis survived. The target multidrug resistant organism was cleared in 88% of subjects evaluated by repeat microbiologic testing. Acute renal failure developed in only two patients (4%).

Conclusions:

Polymyxin B has acceptable effectiveness against nosocomial multidrug resistant Gram-negative sepsis. The associated nephrotoxicity has been found to be significantly lower than previously reported even in patients with background renal impairment and established risk factors of renal failure.     

Bedside echocardiography is useful in assessing children with fluid and inotrope resistant septic shock

Objective:

To report changes in the cardiovascular management of fluid and inotropic resistant septic shock in children based on echocardiography.

Design:

Retrospective case series.

Setting:

Tertiary care Pediatric Intensive Care Unit (PICU), Chennai.

Patients:

Twenty-two patients with unresolved septic shock after 60 ml/kg fluid plus inotropic agents in the first hour.

Interventions:

Bedside echocardiography (echo) within 6 h of admission to the PICU.

Results:

Over a 28-month period, of 37 patients with septic shock, 22 children remained in shock despite 60 ml/kg fluid and dopamine and/or dobutamine infusions as per guidelines. On clinical exam, 12 patients had warm shock and ten had cold shock, however, six exhibited an unusual pattern of cold shock with wide pulse pressures on invasive arterial monitoring. The most common echocardiographic finding was uncorrected hypovolemia in 12/22 patient while ten patients had impaired left ± right ventricular function. Echocardiography permitted an appreciation of the underlying disordered pathophysiology and a rationale for adjustment of treatment. Shock resolved in 17 (77%) and 16 patients (73%) survived to discharge.

Conclusions:

Bedside echo provided crucial information that was not apparent on clinical assessment and affords a simple noninvasive tool to determine the cause of low cardiac output in patients who remain in shock despite 60 ml/kg fluid and inotropic support. Most patients in our series had vasodilatory shock with wide pulse pressures and most common finding on echo was uncorrected hypovolemia. The echo findings allowed adjustment of therapy which was not possible based on clinical examination alone.     

Oral and systemic administration of beta-glucan protects against lipopolysaccharide-induced shock and organ injury in rats

beta-Glucans are glucose polymers with a variety of stimulatory effects on the immune system. The objective of this study was to determine the effect of prophylactic oral administration of soluble Saccharomyces cerevisiae-derived beta-1,3/1,6-glucan (SBG) on the outcome of experimental endotoxaemia and shock-associated organ injury. Male Wistar rats were pretreated with SBG orally (SBGpo, 20 mg/kg/day) for 14 days, subcutaneously (SBGsc, 2 mg/kg/day) for 3 days, or vehicle (placebo). Rats were anaesthetized and subjected to endotoxaemia by intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (6 mg/kg) or saline infusion (sham). We observed significant levels of plasma beta-glucan in the SBGpo group (P<0 x 5), although the SBGsc group had levels approximately 40-fold higher despite a 10-fold lower dose. SBG prophylaxis caused enhanced blood pressure recovery following LPS-induced blood pressure collapse. Oral treatment with SBG attenuated the LPS-induced rise in plasma creatinine levels (P<0 x 05), indicating protection against renal injury. SBG also attenuated the plasma levels of aspartate aminotransferase and alanine aminotransferase (SBGpo, P<0 x 01; SBGsc, P<0 x 01), indicating protection against LPS-induced hepatic injury. A moderate increase in baseline interleukin (IL)-1beta levels was observed in the SBGsc group (P< 0 x 05). In the LPS-challenged rats, plasma levels of proinflammatory cytokines was moderately reduced in both SBG-treated groups compared to placebo. SBG treatment, particularly oral administration, had a striking effect on the haemodynamics of LPS-treated rats, although only a minute fraction of the orally administered beta-glucan translocated to the circulation. Enhanced organ perfusion may thus be responsible for the attenuated levels of indicators of kidney and liver injury seen in SBG-treated rats.     

持续低效血液透析与连续性肾脏替代治疗在感染性休克急性肾损伤患者的疗效对比

目的对比研究持续低效血液透析(SLED)与连续性肾脏替代治疗(CRRT)在感染性休克急性肾损伤(AKI)患者中治疗效果。方法选择60例感染性休克AKI的患者,其中男性36例,女性24例;年龄28~71岁,平均年龄49.56岁。随机分为SLED组(30例)和CRRT组(30例)。两组患者均按《2016国际严重脓毒症及脓毒症休克诊疗指南》治疗,在此基础上分别予以SLED(每次治疗8~10 h,24 h后重复治疗,每例患者至少进行3次以上)和CRRT[模式为连续性静脉-静脉血液滤过,治疗剂量35~40 mL/(kg·h),初始24 h持续治疗,然后根据病情调整治疗时间]。分别观察两组患者治疗前后的血肌酐、pH、钾离子、每天液体平衡、急性生理与慢性健康评价Ⅱ(APACHEⅡ)评分及治疗期间血流动力学稳定性的变化。并比较两组患者的重症监护病房(ICU)住院时间、90 d病死率。结果与CRRT组比较,SLED组治疗后12 h和治疗后5 d的血肌酐、钾离子水平均显著低于CRRT组(P<0.05)。与CRRT组APACHEⅡ评分[(14.78±3.79)分]比较,SLED组治疗后5 d的APACHEⅡ评分[(10.45±3.02)分]明显低于CRRT组(P<0.05)。两组患者治疗期间,SLED组具有与CRRT组相近的血流动力学稳定性(P>0.05)。其中,SLED组血管加压药指数(VI)为20.32±5.18,血管加压药依赖性(VD)为(22.08±4.41)%;CRRT组VI为21.05±5.63,VD为(22.67±4.95)%。SLED组患者ICU住院时间[(15.32±3.65)d]显著短于CRRT组[(19.76±4.18)d],差异有统计学意义(P<0.05)。但两组患者90 d病死率差异无统计学意义(33.33%vs 36.67%;P>0.05)。结论SLED治疗感染性休克AKI患者的疗效确切,且在治疗期间血流动力学稳定性方面并不亚于CRRT。     

Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study

CytoSorb^® (CytoSorbents Corporation, USA) is a novel sorbent hemoadsorption device for cytokine removal. The aim of this study was to examine the clinical use of CytoSorb^® in the management of patient with septic shock. We used this device as an adjuvant to stabilize a young patient with multi-organ failure and severe sepsis with septic shock. A 36-year-old female patient was hospitalized with the complaints of malaise, general body ache, and breathing difficulty and had a medical history of diabetes mellitus type II, hypertension, obstructive sleep apnea, hypothyroidism and morbid obesity. She was diagnosed to have septic shock with multi-organ dysfunction (MODS) and a low perfusion state. CytoSorb^® hemoadsorption column was used as an attempt at blood purification. Acute physiology and chronic health evaluation score, MODS score, and sequential organ failure assessment score were measured before and after the device application. CytoSorb application as an adjuvant therapy could be considered in septic shock.