连续性肾脏替代疗法叠加全血吸附改善脓毒性休克患者心肌抑制的疗效研究

目的探讨连续性肾脏替代疗法（CRRT）叠加全血吸附对脓毒性休克患者心肌抑制的改善效果。 方法选择2016年5月至2019年6月收治于绍兴市人民医院重症医学科、心脏指数（CI）< 3.0 L·min^-1·m^-2的60例脓毒性休克患者,按随机区组法分为对照组（30例）与试验组（30例）,两组患者按照脓毒症/脓毒性休克标准化操作程序治疗,试验组在标准治疗基础上加用CRRT +全血吸附,连续治疗3 d。所有入选病例均应用脉波指示剂连续心排出量监测进行血流动力学监测,记录并评价两组患者入组时及治疗后第3、5天的CI、中心静脉压（CVP）、血管外肺水指数（EVLWI）、日去甲肾上腺素剂量、日液体总量及急性病生理学和长期健康评价（APACHE）Ⅱ评分。 结果两组脓毒性休克患者在不同时间点CI、CVP、EVLWI、日去甲肾上腺素剂量、日液体总量和APACHEⅡ评分的比较,差异均有统计学意义（F = 12.543、10.213、12.840、9.765、10.821、19.466,P均< 0.05）。两组患者入组时上述各指标的比较,差异均无统计学意义（P均> 0.05）;治疗后CI均有不同程度改善,试验组第3、5天CI均高于对照组[（3.0 ± 1.7）L·min^-1·m^-2 vs.（2.6 ± 1.6）L·min^-1·m^-2,（3.2 ± 1.8）L·min^-1·m^-2 vs.（2.7 ± 1.8）L·min^-1·m^-2,P均< 0.05];两组患者的CVP治疗后均呈现下降趋势,且试验组第3、5天CVP值均显著低于对照组[（11.9 ± 5.9）cmH₂O vs.（13.5 ± 3.1）cmH₂O,（10.6 ± 3.7）cmH₂O vs.（12.6 ± 2.6）cmH₂O,P均< 0.05];两组患者EVLWI在治疗后第3、5天回落至正常水平,且治疗后第3天试验组EVLWI显著低于对照组[（9.8 ± 2.4）mL/kg vs.（11.4 ± 3.3）mL/kg,P < 0.05];治疗后第3、5天试验组日去甲肾上腺素剂量[（11.4 ± 3.4）mg vs.（18.9 ± 5.3）mg,（7.5 ± 2.1）mg vs.（13.2 ± 3.2）mg,P均< 0.05]和日液体总量[（2 954 ± 537）mL vs.（3 624 ± 453）mL,（2 446 ± 484）mL vs.（3 243 ± 675）mL,P均< 0.05]均少于对照组。两组患者APACHEⅡ评分治疗后呈下降趋势,试验组第3、5天APACHEⅡ评分均显著低于对照组[（13 ± 4）分vs.（18 ± 4）分,（11 ± 3）分vs.（13 ± 4）分,P均< 0.05]。 结论CRRT叠加全血吸附可在早期改善脓毒性休克患者心肌抑制状态,一定程度上改善患者预后。     

Extended drotrecogin alfa (activated) treatment in patients with prolonged septic shock

Objective  To determine the efficacy and safety of extended drotrecogin alfa (activated) (DAA) therapy. Design  Multicentre, randomised, double-blind, placebo-controlled study. Setting  Sixty-four intensive care units in nine countries. Patients  Adults with severe sepsis and vasopressor-dependent hypotension after a 96-h infusion of standard DAA. Interventions  A total of 193 patients received an intravenous infusion of extended DAA 24 μg/kg/h or sodium chloride placebo for a maximum of 72 h. Measurements and results  At extended therapy initiation (baseline), DAA-group patients had lower protein C levels (P = 0.23) and higher vasopressor requirements, particularly for the primary vasopressor used, norepinephrine (P = 0.03), compared with placebo-group patients. DAA treatment did not result in a difference in the primary outcome of time to resolution of vasopressor-dependent hypotension versus placebo (P = 0.419). However, few patients reached resolution (DAA 34%, placebo 40%) as most continued to require vasopressor support after 72 additional hours of treatment. Treatment did not reduce 28-day all-cause mortality and in-hospital mortality or improve organ function compared with placebo, although there was a lower percentage change in D-dimers (P < 0.001) and increases in protein C levels were numerically greater on extended infusion. There was no difference in serious adverse events including bleeding events. Conclusions  Extended DAA treatment did not result in more rapid resolution of vasopressor-dependent hypotension, despite demonstrating anticipated biological effects on D-dimer and protein C levels. A reduced planned sample size combined with baseline imbalances in protein C levels and vasopressor requirements may have limited the ability to demonstrate a clinical benefit. An erratum to this article can be found at     

Role of vasopressin in the management of septic shock

Vasopressin is a potent vasopressor for improving organ perfusion during septic shock. The rationale for the use of vasopressin is its relative deficiency of plasma levels and hypersensitivity to its vasopressor effects during septic shock. Growing evidence suggests that low-dose (<0.04 U/min) vasopressin is safe and effective for the treatment of vasodilatory shock. Although it is being used more frequently, there are no randomized clinical trials comparing vasopressin as a first-line agent to commonly used vasopressors. However, vasopressin causes arterial smooth muscle cell contraction through a non-catecholamine receptor pathway, thus it represents an attractive adjunct to the management of septic shock, especially when catecholamines are ineffective.This work was supported by the American Heart Association, HL-66211, and the Evanston Northwestern Healthcare Research Institute.     

血液灌流联合连续性血液滤过治疗脓毒血症并急性肾损伤

目的评价采用中性树脂的血液灌流联合连续性血液滤过治疗脓毒血症合并急性肾损伤(AKI)的临床疗效及安全性。方法回顾性分析广州市第一人民医院2008年至2010年脓毒症合并AKI患者78例,其中联合治疗组(L组)32例,单纯血液滤过组(S组)46例。L组先行血液灌流治疗,再行血液滤过治疗,S组仅接受血液滤过治疗。2组患者分别于治疗前及治疗第24、48、72h监测APACHEⅡ评分、氧合指数(OI)、平均动脉压(MAP)、多巴胺用量(DA)、血肌酐水平(Scr)、C反应蛋白水平(CRP)、血清白介素-6(IL-6)和白介素-10(IL-10)水平、血红蛋白浓度(Hb)和血小板计数(Plt)。观察2组以上指标的变化。结果 L组患者均能耐受血液灌流治疗,无不良并发症发生。与治疗前比较,2组在治疗第24、48、72h时,其APACHEⅡ评分、DA、Scr、CRP及血清IL-6水平均显著下降(P<0.05),OI、MAP均明显上升(P<0.05)。在治疗第24、48、72h时,L组的APACHEⅡ评分、DA、Scr、CRP及血清IL-6水平均低于S组(P<0.05),而OI和MAP均高于S组(P<0.05),但2组间IL-10水平、血红蛋白浓度及血小板计数比较均无差异(P>0.05)。结论采用中性树脂的血液灌流联合连续性血液滤过可降低脓毒症患者APACHEⅡ评分、多巴胺用量、CRP及IL-6水平,提高OI及MAP,缩短患者ICU停留时间,而对30d生存率、IL-10水平、Hb浓度及Plt计数无影响。     

Persistently low plasma thioredoxin is associated with meningococcal septic shock in children

Objective To compare plasma levels of thioredoxin (Trx), TNF-α and IL-1β in children during the acute phase of meningococcal septic shock (MSS) and in convalescence. Design and setting Retrospective, observational study in the paediatric intensive care unit of a postgraduate teaching hospital. Patients Thirty-five children requiring intensive care for meningococcal sepsis; paired convalescent samples from 30 survivors (median interval between samples 62 days); 25 healthy control children. Measurements and results Plasma Trx levels were significantly lower in the children with MSS, both during the acute illness (5.5 ng/ml, IQR 1.4–11.4) and in convalescence (2.5 ng/ml, IQR 0.4–6.9) than controls (18.8 ng/ml, IQR 7.9–25.0). Levels of IL-1β and TNF-α were higher in patients with acute MSS (30.3 pg/ml, IQR 3.6–63.6, and 145.9 pg/ml, IQR 31.8–278.1 respectively) than controls (3.7 pg/ml, IQR 0–36.9, and 23.8 pg/ml, IQR 0–124.3, respectively). Levels fell in convalescence (3.7 pg/ml, IQR 0–25.5, 3.7 pg/ml, IQR 0–304.8, respectively). Plasma Trx was higher in non-survivors, albeit a small group (n = 5), than in survivors (n = 30). Trx, IL-1β, and TNF-α levels were not correlated with predicted mortality as assessed by the paediatric risk of mortality (PRISM) score. Conclusions Children with MSS exhibit persistently low plasma levels of Trx during acute illness and in convalescence.     

乌司他丁对脓毒性休克患者细胞因子的影响

目的探讨乌司他丁(UTI)对脓毒性休克患者细胞因子的影响。方法采用前瞻对照研究。78例脓毒性休克患者随机分为对照组和治疗组各39例,两组均行常规抗休克和病因治疗。治疗组用乌司他丁20万U溶于20 ml 0．9%生理盐水中静脉注射,每24 h一次,连续3 d;对照组则以等量生理盐水作为安慰对照。分别于不同时相(静脉注射UTI前、后24 h、48 h和72 h)测试血清肿瘤坏死因子-α(TNF-α)、IL-1、IL-6、IL-8和SOD水平。结果与对照组相比,治疗组应用乌司他丁后不同时相点的TNF-α、IL-1、IL- 6、IL-8均明显降低(P＜0．05,P＜0．01),而SOD显著增加(P＜0．05,P＜0．01)。结论乌司他丁可降低脓毒性休克患者TNF-α、IL-1、IL-6和IL-8的水平并提高SOD活性,从而达到保护器官的作用。     

The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial

Objective  To determine if statin therapy reduces the incidence of severe sepsis and the levels of inflammatory cytokines in patients with acute bacterial infection. Design  Double-blind placebo controlled randomized clinical trial. Setting  Department of medicine and medical intensive care unit in a tertiary university medical center. Patients and participants  A total of 83 patients with suspected or documented bacterial infection were enrolled. We randomly assigned 42 patients to receive 40 mg of simvastatin orally, followed by 20 mg of simvastatin, and 41 to receive matching placebo. Measurements and results  The study was prematurely terminated due to slow recruitment rate. Here we report the analysis of the secondary outcome: change in cytokines levels at 72 h. Both groups were evenly matched in terms of co-morbidity and severity of illness on admission. Four of the 83 patients enrolled developed severe sepsis, two in each group. No difference was observed in other clinical variables and there were no mortalities. Cytokine levels were randomly assessed in 40 patients (20 in each group). Both TNF-α and IL-6 levels were significantly reduced in the simvastatin group (p = 0.02 and p = 0.02, respectively), while no such difference was observed in the placebo group (p = 0.35 and 0.39, respectively). Conclusions  Statin therapy may be associated with a reduction in the levels of inflammatory cytokines in patients with acute bacterial infections. Large controlled trials will determine if this reduction will translate into a clinical benefit. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Diaphragm function in patients with sepsis and septic shock: A longitudinal ultrasound study

BackgroundPrevious literature on the determinants of diaphragm dysfunction in septic patients is limited. The goal of this study is to assess diaphragm dysfunction in terms of its prevalence and its potential associated factors in septic intensive care unit (ICU) patients.MethodsThis prospective and observational study was conducted between June 2015 and July 2019. Ultrasound measures of diaphragm thickness were performed daily on septic patients. The primary outcome was the prevalence of diaphragm dysfunction at baseline and during the ICU stay. The secondary outcome was the diaphragm thickness. Possible associated factors were prospectively recorded.ResultsFifty patients were enrolled in the study. The prevalence of diaphragm dysfunction was 58%. No diaphragm atrophy was found during the ICU stay. Diaphragm dysfunction was associated with the alteration of consciousness, intra-abdominal sepsis, hypnotics and opioids, and mechanical ventilation. Administration of hypnotics, opioids, and steroids was associated with a decreased diaphragm thickening fraction. Diaphragm dysfunction had no impact on patient outcomes.ConclusionsOur data reveal a high prevalence of diaphragm dysfunction in septic patients at the onset of sepsis. Administration of hypnotics, opioids, and steroids was associated with the alteration of diaphragm function as well as intra-abdominal sepsis.     

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock

Objective To develop management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis.Design The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built upon a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along 5 levels to create recommendation grades from A–E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management.Participants Participants included 44 critical care and infectious disease experts representing 11 international organizations.Results A total of 46 recommendations plus pediatric management considerations.Conclusions Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that will hopefully translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually, and even more rapidly when some important new knowledge becomes available.Electronic Supplementary Material Supplementary material is available in the online version of this articel at This article is published jointly with Critical Care MedicineChairs: R. Phillip Dellinger, MD*; Henry Masur, MD; Jean M. Carlet, MD; Herwig Gerlach, MD, PhD**. Committee members: Richard J. Beale, MD**; Marc Bonten, MD; Christian Brun-Buisson, MD; Thierry Calandra, MD; Joseph A. Carcillo, MD; Jonathan Cohen, MD**; Catherine Cordonnier, MD; E. Patchen Dellinger, MD; Jean-Francois Dhainaut, MD, PhD; Roger G. Finch, MD; Simon Finfer, MD; Francois A. Fourrier, MD; Juan Gea-Banacloche MD; Maurene A. Harvey, RN, MPH**; Jan A. Hazelzet, MD; Steven M. Hollenberg, MD; James H. Jorgensen, PhD; Didier Keh, MD; Mitchell M. Levy*, MD; Ronald V. Maier, MD; Dennis G. Maki, MD; John J. Marini, MD; John C. Marshall, MD; Steven M. Opal, MD; Tiffany M. Osborn, MD; Margaret M. Parker, MD**; Joseph E. Parrillo, MD; Graham Ramsay, MD*; Andrew Rhodes, MD; Jonathan E. Sevransky, MD; Charles L. Sprung, MD, JD**; Antoni Torres, MD; Jeffery S. Vender, MD; Jean-Louis Vincent, MD, PhD**; Janice L. Zimmerman, MD. Associate members: E. David Bennett, MD; Pierre-Yves Bochud, MD; Alain Cariou, MD; Glenn S. Murphy, MD; Martin Nitsun, MD; Joseph W. Szokol, MD; Stephen Trzeciak, MD; Christophe Vinsonneau, MD. *Executive Committee, Surviving Sepsis Campaign. **Steering Committee, Surviving Sepsis Campaign.Sponsoring organizations: American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; American Thoracic Society; Australian and New Zealand Intensive Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Society of Critical Care Medicine; Surgical Infection Society.The Surviving Sepsis Campaign is administered jointly by the European Society of Intensive Care Medicine, International Sepsis Forum, and the Society of Critical Care Medicine, and is supported in part by unrestricted educational grants from Baxter Bioscience, Edwards Lifesciences, and Eli Lilly and Company (majority sponsor).The authors and the publisher have exercised great care to ensure that drug dosages, formulas, and other information presented in this book are accurate and in accord with the professional standards in effect at the time of publication. Readers are, however, advised to always check the manufacturers product information sheet that is packaged with the respective products to be fully informed of changes in recommended dosages, contraindications, and the like before prescribing or administering any drug.     

Reversal of refractory septic shock with drotrecogin alpha (activated)

Objective  We previously reported that early continuous veno-venous hemodiafiltration (CVVHDF) enables rapid identification of a subgroup of patients with “refractory” septic shock and a 100% risk of death. The objective of this study was to investigate whether early administration of drotrecogin alpha (activated) (DrotAA) to this selected subgroup of septic patients at extremely high risk of death would significantly improve prognosis. Method  Prospective observational study in a medical intensive-care unit of a University Hospital. Twenty-three patients with refractory septic shock were included. “Refractory” shock was defined as persistent circulatory failure despite adequate circulatory support, associated with persisting lactic acidosis despite early CVVHDF. Response to CVVDHF was assessed after 6 h of this continuous procedure. Patients selected by this strategy received DrotAA infusion for four days. Results  The 28-day mortality rate of the 23 patients was 39%. No difference was observed at inclusion between survivors and nonsurvivors. In patients who finally survived, 12 h of DrotAA infusion was associated with a significant decrease in lactic acidosis and in norepinephrine dose. Conclusion  DrotAA therapy was associated with unexpectedly high 28-day survival in patients with “refractory” septic shock.     

高容量血液滤过对老年感染性休克合并MODS患者细胞因子的影响

目的观察高容量血液滤过(HVHF)对老年感染性休克合并多脏器功能不全综合征(MODS)患者细胞因子的影响。方法对22例患者行HVHF治疗24h,治疗前和治疗后1、3、6、9、12、18和24h分别采用放免法测定血液和超滤液中TNFα、IL1β、IL6、IL10的含量。结果22例患者均完成HVHF治疗。与治疗前相比,治疗后APACHEⅡ评分、MODS评分显著改善(P<0.01)。第28天存活10例,病死率为54.5%。血液中炎症介质浓度均有明显的下降(P<0.01),其效应在9h时最为明显(P<0.01),超滤液中检测到TNFα、IL1β,未发现IL6、IL10。结论HVHF有明显的清除老年感染性休克合并MODS患者血液中炎症介质的作用。其机制可能为膜的吸附和对流,在高流通量条件下,适时更换血滤器仍然很有必要。     

Early alterations of B cells in patients with septic shock

Introduction

It has recently been proposed that B lymphocytes are involved in sepsis pathogenesis. The goal of this study is to investigate potential abnormalities in a subset distribution and activation of circulating B lymphocytes in patients with septic shock.

Methods

This observational prospective study was conducted in a medical-surgical ICU. All patients with septic shock were eligible for inclusion. B-cell phenotypes (CD19+CD69+, CD19+CD23+, CD19+CD5+, CD19+CD80, CD19+CD86+, CD19+CD40 and CD19+CD95+) were assessed by quantitative flow cytometry upon admission to the ICU and 3, 7, 14 and 28 d later.

Results

Fifty-two patients were included. Thirty-six healthy volunteers matched for age and sex were used as controls. The patients had lymphopenia that was maintained during 28 d of follow-up. In patients with septic shock who died, the percentage of CD19+CD23+ was lower during the 7 d of follow-up than it was in survival patients. Moreover, the percentage of CD80+ and CD95+ expression on B cells was higher in patients who died than in survivors. Receiver operating characteristic curve analysis showed that a CD19+CD23+ value of 64.6% at ICU admission enabled discrimination between survivors and nonsurvivors with a sensitivity of 90.9% and a specificity of 80.0% (P = 0.0001).

Conclusions

Patients with septic shock who survive and those who don''t have different patterns of abnormalities in circulating B lymphocytes. At ICU admission, a low percentage of CD23+ and a high of CD80+ and CD95+ on B cells were associated with increased mortality of patients with septic shock. Moreover, a drop in circulating B cells persisted during 28 d of ICU follow-up.     

High-dose CytoSorb hemoadsorption is associated with improved survival in patients with septic shock: A retrospective cohort study

Background and purposeHemoadsorption with CytoSorb® offers a possible therapeutic approach in septic shock, but modes of application and dosing are still undetermined.Materials and methodsData from surgical patients with septic shock, treated with hemoadsorption adjunctive to renal replacement therapy were analyzed retrospectively. The 28-day mortality was compared to predicted mortality.ResultsIn 70 patients (70.6 ± 13.3 years), hemoadsorption was applied for 85.6 ± 53.8 h. The APACHE ll (30.2 ± 6.3) calculated to a predicted mortality of 73.3%, while the observed mortality was significantly lower (50%, p < 0.05).The amount of blood purified was higher in survivors than in non-survivors (8.5 ± 4.4 vs. 6.1 ± 3.6 l/kgBW, p = 0.017). We identified three clusters of <6 l/kgBW, 6-13 l/kgBW and ≥ 13 l/kgBW with a linear dose-response relation between blood purification volume and survival, which was best in the highest volume cluster (83.3%; p = 0.045).ConclusionsThe application of CytoSorb® seems to be effective in various conditions of septic shock. In a cohort of most severely ill patients the observed mortality was lower than predicted and decreased linearly with blood purification volumes inadvertently exceeding 6 l/kg BW. These results suggest that hemoadsorption might improve survival provided that the applied dose is high enough.     

Procalcitonin (PCT) in patients with abdominal sepsis

Background To assess the accuracy of procalcitonin as a measure of severity in patients with septic abdominal illnesses and the sepsis syndrome, to compare measurements with those of other inflammatory mediators, and to predict outcome. Methods We carried out a prospective clinical study from 246 patients with infective or septic episodes confirmed at laparotomy and 66 patients undergoing elective operations who acted as controls. Specimens of blood for measurement of cytokine concentrations determination were obtained daily from septic patients. In the control group specimens were obtained before operation, at the end of operation, and on each of the following days until normal recovery (day 10). Every two weeks up to 3 months for patients with metastases, who were being followed up. Results Compared with other cytokines such as tumor necrosis factor αa and interleukin 6 procalcitonin was closely related to the development of infective and septic complications. 59 of 246 patients (24%) with sepsis died. Procalcitonin concentrations preoperatively [median 2.05 compared with 4.2 ng/ml (p=0.08)] (Mann-Whitney U-test) did not differ, but those on the days 1,4 and at the end differed significantly [day 1∶4.9 compared with 13.8 ng/ml (p<0.01); day 4∶4.8 compared with 13.0 ng/ml (p<0.01) and 0.4 compared with 13.25 ng/ml (p<0.01) at the end of the study]. In the control group only 7 (1.6%) of all blood samples, were detected outside the normal range (up to 0.8 ng/ml). Conclusions Procalcitonin is a new indicator of infection and sepsis. TNF and IL-6 concentrations always rise after major operations and fall in the absence of infection, indicating operative trauma. Procalcitonin is sensitive in detecting infective complications. Under routine conditions the procalcitonin concentrations seems to be valid, reproducible and detectable.     

Increased colorectal permeability in patients with severe sepsis and septic shock

Objective To develop a method for the assessment of colorectal permeability in septic patients.Design and setting Observational study in ICUs at two university hospitals.Participants Nine patients with septic shock and abdominal focus of infection, 7 with severe sepsis and pulmonary focus and 8 healthy subjects.Measurements and results Colorectal permeability was assessed as the initial appearance rate of ^99mTc-DTPA in plasma after instillation into the rectal lumen and as the cumulative systemic recovery at 1 h. To calculate the latter, volume of distribution and renal clearance of ^99mTc-DTPA was estimated by an i. v. bolus of ⁵¹Cr-EDTA. The initial rate of permeability was increased in patients with septic shock and severe sepsis compared with controls [29.0 (3.7–83.3), 20.6 (3.6–65.5) and 6.0 (2.2–9.6) cpm ml⁻¹ min⁻¹, respectively, p < 0.05)] with a positive linear trend (r ² = 0.27, p = 0.01) and correlated to L-lactate concentrations in the rectal lumen (r ² = 0.39, p < 0.05). The cumulative permeability was also increased in patients with septic shock and severe sepsis compared with controls [2.07 (0.05–15.7), 0.32 (0.01–1.2) and 0.03 (0.01–0.06)‰, respectively, p < 0.01] and correlated to the initial permeability rate (r ² = 0.26, p = 0.01).Conclusions In septic patients, the systemic recovery of a luminally applied marker of paracellular permeability was increased and related to the luminal concentrations of L-lactate and possibly to disease severity. This suggests that the assessment of colorectal permeability by systemic recovery of ^99mTc-DTPA is valid and that metabolic dysfunction of the mucosa contributes to increased permeability of the large bowel in patients with severe sepsis and septic shock.     

Cytokine removal and cardiovascular hemodynamics in septic patients with continuous venovenous hemofiltration

Objectives: To determine whether continuous venovenous hemofiltration leads to extraction of tumor necrosis factor alpha (TNFα) and cytokines from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and the removal rate of these cytokines and their effect on serum cytokine concentrations. Design: Prospective, controlled study in patients with continuous venovenous hemofiltration (24 l/24 h) using a polysulphone membrane in patients with acute renal failure. Patients: 33 ventilated patients with acute renal failure of septic (n = 18) and cardiovascular origin (n = 15) were studied. Interventions: Hemodynamic monitoring and collection of blood and ultrafiltrate samples before and during the first 72 h of continuous hemofiltration. Measurements and main results: Cardiovascular hemodynamics (Swan-Ganz catheter), Acute Physiology and Chronic Health Evaluation II score, creatinine, electrolytes, and blood urea nitrogen were recorded daily. Cytokines (TNFα, TNFα-RII, interleukin (IL) 1β , IL1RA, IL2, IL2R, IL6, IL6R, IL8, IL10) were measured in prefilter blood and in ultrafiltrate immediately preceding and 12, 24, 48, and 72 h after initiating continuous venovenous hemofiltration (CVVH). Septic patients showed elevated cardiovascular values for cardiac output (7.2 ± 2.1 l/min), cardiac index (4.2 ± 1.3 l/min per m²), and stroke volume (67 ± 23 ml) and reduced values for systemic vascular resistance (540 ± 299 dyn · s · cm^{− 5}). All hemodynamic values normalized within the first 24 h after initiating CVVH treatment. TNFα was 1833 ± 1217 pg/ml in septic patients and 42.9 ± 6.3 pg/ml in nonseptic patients (p < 0.05) prior to CVVH. TNFα was detected in ultrafiltrate but did not decrease in blood during treatment with CVVH. There was no difference in IL 1β between septic (3.8 ± 1.9 pg/ml) and nonseptic patients (1.7 ± 0.5 pg/ml). No significant elimination of cytokines was achieved in the present study by CVVH treatment. Conclusions: These findings demonstrate that CVVH can remove TNFα and special cytokines from the circulation of critically ill patients. Cardiovascular hemodynamics seemed to improve in septic patients after induction of hemofiltration treatment, although there was no evidence that extracorporeal removal of cytokines achieved a reduction in blood levels. The study indicates that low volume continuous hemofiltration with polysulphone membranes in patients with acute renal failure is not able to induce significant removal of cytokines. Received: 12 February 1996 Accepted: 27 November 1996