Objective:An initial phase II trial to investigate the safety and therapeutic effect of the endotoxin adsorber system EN 500 in septic patients suffering from presumed Gram-negative infection. Design:Open, controlled, prospective, randomized, multiple-center, parallel-group clinical trial. Setting:Intensive care units of 31 university-affiliated and community hospitals in Europe. Patients:One hundred forty-five patients with a clinical diagnosis of severe sepsis or septic shock due to suspected Gram-negative infection. Interventions:Patients were randomized to receive either standard therapy alone for sepsis (n = 76) or standard therapy plus extracorporeal endotoxin adsorption (n = 67) daily for the first 4 days following study entry. Measurements and Main Results:The primary end point was the proportion of responders (defined as a decrease in Acute Physiology and Chronic Health Evaluation II score by ≥4 points from study entry to day 4). Secondary outcomes were the Sequential Organ Failure Assessment score and its components, length of intensive care unit stay, survival rate, and safety of the adsorber treatment. Patient characteristics at entry were well balanced between the two treatment groups, except for a higher Sequential Organ Failure Assessment score in the adsorber group. On all-subjects-treated analysis, 65% of the adsorber group were responders vs. 57% for the standard (p = .389). A planned interim analysis restricted further enrollment to patients with peritonitis, in whom a slightly higher proportion of responders was observed with the adsorber treatment (69%) vs. standard treatment (54%, p = .159). There were no differences in survival, but adsorption treatment in peritonitis patients was associated with trends toward a reduction in length of intensive care unit stay and a more rapid decline in plasma endotoxin concentrations. There was a significantly greater reduction in platelet count with the adsorber; however, this did not require extra treatment. Conclusions:The endotoxin adsorber system did not result in a significantly improved primary end point in patients with presumed Gram-negative sepsis. In patients with peritonitis, the adsorber treatment likewise did not result in significantly improved Acute Physiology and Chronic Health Evaluation II scores. There were no clinically important side effects. These results provide encouragement for further study of adsorber treatment in patients with high likelihood of Gram-negative sepsis (e.g., peritonitis).

Objective: To evaluate the performance of total maximum sequential organ failure assessment (SOFA) score and a derived measure, delta SOFA (total maximum SOFA score minus admission total SOFA) as a descriptor of multiple organ dysfunction/failure in intensive care. Design: Prospective, multicentre and multinational study. Setting: Forty intensive care units (ICUs) from Australia, Europe, North and South America. Patients: Data on 1,449 patients, evaluated at admission and then consecutively every 24 h until ICU discharge (11,417 records) during May 1995. Excluded from data collection were all patients with a length of stay in the ICU less than 2 days following uncomplicated scheduled surgery. Main outcome measure: Survival status at ICU discharge. Interventions: The collection of raw data necessary for the computation of a SOFA score on admission and then every 24 h, and basic demographic and clinical statistics. Measurements and main results: Mean total maximum SOFA score presented a very good correlation to ICU outcome, with mortality rates ranging from 3.2 % in patients without organ failure to 91.3 % in patients with failure of all the six organs analysed. A maximum score was reached 1.1 ± 0.2 days after admission for all the organ systems analysed. The total maximum SOFA score presented an area under the ROC curve of 0.847 (SE 0.012), which was significantly higher than any of its individual components. The cardiovascular score (odds ratio 1.68) was associated with the highest relative contribution to outcome. No independent contribution could be demonstrated for the hepatic score. No significant interactions were found. Principal components analysis demonstrated the existence of a two-factor structure that became clearer when analysis was limited to the presence or absence of organ failure (SOFA score ≥ 3 points) during the ICU stay. The first factor comprises respiratory, cardiovascular and neurological systems and the second coagulation, hepatic and renal systems. Delta SOFA also presented a good correlation to outcome. The area under the receiver operating characteristic (ROC) curve was 0.742 (SE 0.017) for delta SOFA, lower than the total maximum SOFA score or admission total SOFA score. The impact of delta SOFA on prognosis remained significant after correction for admission total SOFA. Conclusions: The results show that total maximum SOFA score and delta SOFA can be used to quantify the degree of dysfunction/failure already present on ICU admission, the degree of dysfunction/failure that appears during the ICU stay and the cumulative insult suffered by the patient. These properties make it a good instrument to be used in the evaluation of organ dysfunction/failure.

AnaesthesiaVolume 53, Issue 12 p. 1141-1143 Free Access Paediatric intensive care — the way ahead? J. Nicholl, J. Nicholl Director, Medical Care Research Unit, University of Sheffield, Sheffield S1 4DA, UK,Search for more papers by this authorS. Willatts, S. Willatts Consultant in Charge of Intensive Care Unit, Bristol Royal Infirmary, Bristol BS21 3NU, UKSearch for more papers by this author J. Nicholl, J. Nicholl Director, Medical Care Research Unit, University of Sheffield, Sheffield S1 4DA, UK,Search for more papers by this authorS. Willatts, S. Willatts Consultant in Charge of Intensive Care Unit, Bristol Royal Infirmary, Bristol BS21 3NU, UKSearch for more papers by this author First published: 06 April 2002 https://doi.org/10.1046/j.1365-2044.1998.00735.xCitations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Citing Literature Volume53, Issue12December 1998Pages 1141-1143 RelatedInformation

Acta Anaesthesiologica ScandinavicaVolume 41, Issue S110 p. 25-26 Anaesthetic lessons to be learnt from confidential inquiries into maternal death Sheila Willatts, Sheila Willatts Sir Humphry Davy Department of Anaesthesia, Bristol Royal Infirmary, Bristol, UKSearch for more papers by this author Sheila Willatts, Sheila Willatts Sir Humphry Davy Department of Anaesthesia, Bristol Royal Infirmary, Bristol, UKSearch for more papers by this author First published: 02 February 2011 https://doi.org/10.1111/j.1399-6576.1997.tb05488.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume41, IssueS110June 1997Pages 25-26 RelatedInformation

OBJECTIVE To investigate the safety, biological effects, and efficacy of the anti-tumor necrosis factor (TNF) antibody fragment, MAK 195F, in a phase II trial in patient with severe sepsis. DESIGN Prospective, randomized, open label, placebo-controlled, dose-ranging, multicenter, multinational clinical trial. SETTING Sixteen academic medical centers' intensive care units in six European countries. PATIENTS One hundred twenty-two patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy. INTERVENTIONS Patients received one of three different doses of the anti-TNF antibody (0.1 mg/kg, 0.3 mg/kg, or 1.0 mg/kg) or placebo; the antibody or placebo was given in nine doses at 8-hr intervals over 3 days. MEASUREMENTS AND MAIN RESULTS There were no significant differences in mortality rates among the groups receiving various doses of the anti-TNF antibody or placebo, but patients with baseline serum interleukin (IL)-6 concentrations of > 1000 pg/mL appeared to benefit from MAK 195F in a dose-dependent fashion. Increased circulating IL-6 concentrations, but not TNF concentrations, were found to be important prognostic indicators for mortality for the patients in the placebo and the two lower dosage groups but not in the high dosage group (1 mg/kg). IL-6 concentrations decreased during the first 24 hrs of treatment in all three anti-TNF groups but not in the placebo group. MAK 195F was well tolerated by all patients. Human antimurine antibodies developed in 40% of the patients receiving the antibody. CONCLUSIONS There was no increase in survival from sepsis for the patients receiving anti-TNF treatment in the overall study population. Retrospective stratification of patients by IL-6 concentrations suggests beneficial effects of the drug for patients with baseline circulating IL-6 concentrations of > 1000 pg/mL. This hypothesis requires validation in a larger, blinded, prospective study.