Epidemiology of sepsis in Germany: results from a national prospective multicenter study

Objective To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. Design Prospective, observational, cross-sectional 1-day point-prevalence study. Setting 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). Patients Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. Measurements and results Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9–13.8%) for sepsis and 11.0% (95% CI, 9.7–12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (≤ 200 beds: 6% and 11.5 days, universities: 19% and 19.2 days, respectively). Conclusions The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76–110 per 100,000 adult inhabitants. To allow better comparison between countries, future epidemiological studies should use standardized study methodologies with respect to sepsis definitions, hospital size, and daily and monthly variability. The named authors wrote this article on behalf of the German Competence Network Sepsis (SepNet) C. Engel and F. M. Brunkhorst contributed equally to this work     

Urinary biomarker of oxidative stress correlating with outcome in critically septic patients

Objective To determine whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients. Design and setting Clinical outcome study in an adult medical intensive care unit (ICU). Patients 85 consecutive septic patients (59 men, 26 women). Measurements and results Patient characteristics and the clinical course were examined. Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality was 25.9% (22/85) and hospital mortality 38.8% (33/85). Survivors' APACHE II scores on days 1 and 3 and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0 ± 7.1 vs. 25.9 ± 8.0; day 3, 15.0 ± 5.8 vs. 23.2 ± 8.3; difference, 6.0 ± 5.5 vs. 1.7 ± 6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8 ± 2.4 vs. 3.0 ± 2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results. Conclusions This is a preliminary study. Excretion of urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, and the APACHE II score were correlated with the outcome of critically septic patients in medical ICU.     

Urinary biomarker of oxidative stress correlating with outcome in critically septic patients

Objective To determine whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients. Design and setting Clinical outcome study in an adult medical ICU. Patients Eighty-five consecutive septic patients: 59 men and 26 women. Measurements and results Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality in these 85 septic patients was 25.9% (n = 22) and hospital mortality 38.8% (n = 33). APACHE II scores of survivors on day 1, on day 3, and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0 ± 7.1 vs. 25.9 ± 8.0; day 3, 15.0 ± 5.8 vs. 23.2 ± 8.3; difference, 6.0 ± 5.5 vs. 1.7 ± 6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8 ± 2.4 vs. 3.0 ± 2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results. Conclusions This is a preliminary study. The excretion of the urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, as the APACHE II score, were correlated with the outcome of critically septic patients in medical ICU. An erratum to this article can be found at     

Mean glucose level is not an independent risk factor for mortality in mixed ICU patients

Objective To find out if there is an association between hyperglycaemia and mortality in mixed ICU patients. Design and setting Retrospective cohort study over a 2-year period at the medical ICU of a university hospital. Measurements Admission glucose, maximum and mean glucose, length of stay, mortality, insulin therapy and Apache-II score. Results In 1085 consecutive patients, ICU- and hospital mortality were 20 and 25%, respectively. The total number of blood glucose measurements was 10.012. Admission glucose was 7.9 ± 4.5 mmol/l (mean ± SD), mean glucose 7.5 ± 2.9 and maximum glucose 10.0 ± 5.4 mmol/l. Median ICU length of stay (LOS) was 3.0 days (range 2.0–6.0 days, IQR), and hospital LOS was 16 days (range 7–32 days). In 28% of patients insulin treatment was started. Median Apache-II score was 13. 68% of patients were mechanically ventilated. Univariate analysis showed an association with ICU mortality for mean glucose (non-survivors 8.6 ± 4.3 vs 7.2 ± 2.4 survivors), maximum glucose (11.7 ± 5.9 vs 9.6 ± 5.2, non-survivors vs survivors, respectively), use of insulin (mortality 29 vs 17% in patients not using insulin) and age (61 vs 55.7 years). Gender and a history of diabetes mellitus were not associated with mortality. In a multivariate model, the Apache-II score was the only variable associated with mortality independent of other variables, including mean blood glucose. Conclusion In this retrospective study mean glucose level was not an independent risk factor for mortality in mixed ICU patients.     

Evaluation of the SOFA score: a single-center experience of a medical intensive care unit in 303 consecutive patients with predominantly cardiovascular disorders

Objective: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score, the total maximum SOFA (TMS) score, and a derived variable, the ΔSOFA (TMS score minus total SOFA score on day 1) in medical, cardiovascular patients as a means for describing the incidence and severity of organ dysfunction and the prognostic value regarding outcome. Design: Prospective, clinical study. Setting: Medical intensive care unit in a university hospital. Patients: A total of 303 consecutive patients were included (216 men, 87 women; mean age 62 ± 12.6 years; SAPS II 26.2 ± 12.7). They were evaluated 24 h after admission and thereafter every 24 h until ICU discharge or death between November 1997 and March 1998. Readmissions and patients with an ICU stay shorter than 12 h were excluded. Main outcome measure: Survival status at hospital discharge, incidence of organ dysfunction/failure. Interventions: Collection of clinical and demographic data and raw data for the computation of the SOFA score every 24 h until ICU discharge. Measurements and main results: Length of ICU stay was 3.7 ± 4.7 days. ICU mortality was 8.3 % and hospital mortality 14.5 %. Nonsurvivors had a higher total SOFA score on day 1 (5.9 ± 3.7 vs. 1.9 ± 2.3, p < 0.001) and thereafter until day 8. High SOFA scores for any organ system and increasing number of organ failures (SOFA score ≥ 3) were associated with increased mortality. Cardiovascular and neurological systems (day 1) were related to outcome and cardiovascular and respiratory systems, and admission from another ICU to length of ICU stay. TMS score was higher in nonsurvivors (1.76 ± 2.55 vs. 0.58 ± 1.39, p < 0.01), and ΔSOFA/total SOFA on day 1 was independently related to outcome. The area under the receiver-operating characteristic curve was 0.86 for TMS, 0.82 for SOFA on day 1, and 0.77 for SAPS II. Conclusions: The SOFA, TMS, and ΔSOFA scores provide the clinician with important information on degree and progression of organ dysfunction in medical, cardiovascular patients. On day 1 both SOFA score and TMS score had a better prognostic value than SAPS II score. The model is closely related to outcome and identifies patients who are at increased risk for prolonged ICU stay. Received: 6 August 1999 Final revision received: 3 January 2000 Accepted: 28 March 2000     

Adrenal insufficiency in severe West Nile Virus infection

Objective To explore adrenal function in severe West Nile virus (WNV) infection.Design and setting Prospective interventional cohort study in a medical ICU of a teaching hospital.Patients Ten consecutive patients (seven men, mean age 64 ± 12 years, mean SAPS II 26 ± 6) with definite diagnosis of WNV related meningoencephalitis and variable proportion of organ/system failure. All patients had fever (mean body temperature 39 ± 1°C) and altered mental status (mean Glasgow Coma Score 11 ± 2). Mean SOFA score was 9 ± 2; eight patients had systemic inflammatory response syndrome, five septic shock, and six acute respiratory failure (usually from central origin) requiring mechanical ventilation.Interventions A short corticotropin test was performed in each patient to assess the adrenal function.Measurements and results Cortisol response was defined as the difference between baseline and corticotropin-stimulated peak. Absolute adrenal insufficiency was defined by a baseline cortisol level below 15 μg/dl (415 nmol/l). Relative insufficiency was defined by a cortisol response of 9 μg/dl (250 nmol/l) or less. Relative adrenal insufficiency, defined by a corticotropin response below 9 μg/dl, was observed in seven while the remaining three had normal cortisol response; six out of these seven died in the ICU. All patients with normal adrenal function survived.Conclusion Adrenal insufficiency is frequent in severe WNV infection and carries a poor outcome. In the absence of specific effective treatment, our data provide a rational to investigate a supplemental corticosteroid treatment in a controlled trial.     

Application of SOFA score to trauma patients

Objective: To assess the ability of the SOFA score (Sequential Organ Failure Assessment) to describe the evolution of organ dysfunction/failure in trauma patients over time in intensive care units (ICU). Design: Retrospective analysis of a prospectively collected database. Setting: 40 ICUs in 16 countries. Patients: All trauma patients admitted to the ICU in May 1995. Main outcome measures and results: Incidence of dysfunction/failure of different organs during the first 10 days of stay and the relation between the dysfunction, outcome, and length of stay. Included in the SOFA study were 181 trauma patients (140 males and 41 females).The non-survivors were significantly older than the survivors (51 years ± 20 vs 38 ± 16 years, p < 0.05) and had a higher global SOFA score on admission (8 ± 4 vs 4 ± 3, p < 0.05) and throughout the 10-day stay. On admission, the non-survivors had higher scores for respiratory ( > 3 in 47 % of non-survivors vs 17 % of survivors), cardiovascular ( > 3 in 24 % of non-survivors vs 5.7 % of survivors), and neurological systems ( > 4 in 41 % of non-survivors vs 16 % of survivors); although the trend was maintained over the whole study period, the differences were greater during the first 4–5 days. After the first 4 days, only respiratory dysfunction was significantly related to outcome. A higher SOFA score, admission to the ICU from the same hospital, and the presence of infection on admission were the three major variables associated with a longer length of stay in the ICU (additive regression coefficients: 0.85 days for each SOFA point, 4.4 for admission from the same hospital, 7.26 for infection on admission). Conclusions: The SOFA score can reliably describe organ dysfunction/failure in trauma patients. Regular and repeated scoring may be helpful for identifying categories of patients at major risk of prolonged ICU stay or death. Received: 3 March 1998 Accepted: 21 December 1998     

Adrenal response in patients with septic shock of abdominal origin: relationship to survival

Objective To evaluate the prognostic value of adrenocortical response to corticotropin in septic shock patients operated on exclusively for an intra-abdominal source of infection. Design and setting Prospective, observational, single-center study in a surgical intensive care unit of a university hospital Patients 118 consecutive septic shock patients undergoing laparotomy or drainage for intra-abdominal infection. Measurements and results Baseline cortisol (t ₀) and cortisol response to corticotropin test (Δ) were measured during the first 24 h following onset of shock. The relationship between adrenal function test results and survival was analyzed as well as the effect of etomidate anesthesia. Cortisol plasma level at t ₀ was higher in nonsurvivors than in survivors (33 ± 23 vs. 25 ± 14 μg/dl), but the response to corticotropin test did not differ between these two subgroups. ROC analysis showed threshold values for t ₀ (32 μg/dl) and Δ (8 μg/dl) that best discriminated survivorsfrom nonsurvivors in our population. We observed no difference in survival at the end of hospital stay using log rank test when patients were separated according to t ₀, Δ, or both. In addition, adrenal function testsand survival did not differ in patients who received etomidate anesthesia (n = 69) during the surgical treatment of their abdominal sepsis. Conclusions In this cohort of patients with abdominal septic shock baseline cortisol level and the response to corticotropin test did not discriminate survivors from nonsurvivors. No deleterious impact of etomidate anesthesia on adrenal function tests and survival was observed in these patients.     

Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial

Objective To compare the effects of arginine-vasopressin (AVP) and norepinephrine (NE) on hemodynamic variables, organ dysfunction, and adverse events in early hyperdynamic septic shock.Design and setting Randomized, controlled, open-label trial.Patients and participants Twenty-three patients with early (12 h) hyperdynamic septic shock in two teaching hospitals.Interventions AVP (0.04–0.20 U min^–1, n = 13) as a single agent or NE (0.1–2.8 μg kg^–1 min^–1, n = 10) infusion for 48 h to achieve mean arterial pressure at or above 70 mmHg.Measurements and results Hemodynamic parameters and Sequential Organ Failure Assessment (SOFA) score were measured. AVP and NE equally increased mean arterial pressure over 48 h, but NE was required in 36% of AVP patients at 48 h. Compared to baseline, AVP increased systemic vascular resistance, decreased exposure to NE, decreased cardiac output by decreasing heart rate, increased creatinine clearance, and improved SOFA score. The PrCO₂ – PaCO₂ difference remained stable throughout the study. One AVP patient developed acute coronary syndrome with dose-dependent ECG changes. Three patients in both groups died during their ICU stay.Conclusion In early hyperdynamic septic shock, the administration of high-dose AVP as a single agent fails to increase mean arterial pressure in the first hour but maintains it above 70 mmHg in two-thirds of patients at 48 h. AVP decreases NE exposure, has no effect on the PrCO₂ – PaCO₂ difference, and improves renal function and SOFA score.This work was supported by the Cardiovascular Critical Care research Network FRSQ and departmental funding.     

Incidence,risk factors and consequences of ICU delirium

Objective Delirium in the critically ill is reported in 11–80% of patients. We estimated the incidence of delirium using a validated scale in a large cohort of ICU patients and determined the associated risk factors and outcomes. Design and setting Prospective study in a 16-bed medical-surgical intensive care unit (ICU). Patients 820 consecutive patients admitted to ICU for more than 24 h. Interventions Tools used were: the Intensive Care Delirium Screening Checklist for delirium, Richmond Agitation and Sedation Scale for sedation, and Numerical Rating Scale for pain. Risk factors were evaluated with univariate and multivariate analysis, and factors influencing mortality were determined using Cox regression. Results Delirium occurred in 31.8% of 764 patients. Risk of delirium was independently associated with a history of hypertension (OR 1.88, 95% CI 1.3–2.6), alcoholism (2.03, 1.2–3.2), and severity of illness (1.25, 1.03–1.07 per 5-point increment in APACHE II score) but not with age or corticosteroid use. Sedatives and analgesics increased the risk of delirium when used to induce coma (OR 3.2, 95% CI 1.5–6.8), and not otherwise. Delirium was linked to longer ICU stay (11.5 ± 11.5 vs. 4.4 ± 3.9 days), longer hospital stay (18.2 ± 15.7 vs. 13.2 ± 19.4 days), higher ICU mortality (19.7% vs. 10.3%), and higher hospital mortality (26.7% vs. 21.4%). Conclusion Delirium is associated with a history of hypertension and alcoholism, higher APACHE II score, and with clinical effects of sedative and analgesic drugs. This article is discussed in the editorial available at:     

A prospective study on adrenal cortex responses and outcome prediction in acute critical illness: results from a large cohort of 203 mixed ICU patients

Objective To assess whether adrenal cortex hormones predict ICU mortality in acute, mixed, critically ill patients. Design and setting Prospective study in consecutive intensive care patients in the general ICU of a teaching hospital. Patients 203 severely ill patients with multiple trauma (n = 93), medical (n = 57), or surgical (n = 53) critical states. Measurements and results Within 24 h of admission in the ICU a morning blood sample was obtained to measure baseline cortisol, corticotropin (ACTH), and dehydropiandrosterone sulfate (DHEAS). Subsequently a low-dose (1 μg) ACTH test was performed to determine stimulated cortisol. The incremental rise in cortisol was defined as stimulated minus baseline cortisol. Overall, 149 patients survived and 54 died. Nonsurvivors were older and in a more severe critical state, as reflected by higher SOFA and APACHE II scores. Nonsurvivors had a lower incremental rise in cortisol (5.0 vs. 8.3 μg/dl and lower DHEAS (1065 vs. 1642 ng/ml) than survivors. The two groups had similar baseline and stimulated cortisol. Multivariate logistic regression analysis revealed that age (odds ratio 1.02), SOFA score (1.36), and the incremental rise in cortisol (0.88) were independent predictors for poor outcome. Conclusions In general ICU patients a blunted cortisol response to ACTH within 24 h of admission is an independent predictor for poor outcome. In contrast, baseline cortisol or adrenal androgens are not of prognostic significance.     

Sepsis mortality prediction based on predisposition,infection and response

Objective To empirically test, based on a large multicenter, multinational database, whether a modified PIRO (predisposition, insult, response, and organ dysfunction) concept could be applied to predict mortality in patients with infection and sepsis. Design Substudy of a multicenter multinational cohort study (SAPS 3). Patients A total of 2,628 patients with signs of infection or sepsis who stayed in the ICU for > 48 h. Three boxes of variables were defined, according to the PIRO concept. Box 1 (Predisposition) contained information about the patient's condition before ICU admission. Box 2 (Injury) contained information about the infection at ICU admission. Box 3 (Response) was defined as the response to the infection, expressed as a Sequential Organ Failure Assessment score after 48 h. Interventions None. Main measurements and results Most of the infections were community acquired (59.6%); 32.5% were hospital acquired. The median age of the patients was 65 (50–75) years, and 41.1% were female. About 22% (n = 576) of the patients presented with infection only, 36.3% (n = 953) with signs of sepsis, 23.6% (n = 619) with severe sepsis, and 18.3% (n = 480) with septic shock. Hospital mortality was 40.6% overall, greater in those with septic shock (52.5%) than in those with infection (34.7%). Several factors related to predisposition, infection and response were associated with hospital mortality. Conclusion The proposed three-level system, by using objectively defined criteria for risk of mortality in sepsis, could be used by physicians to stratify patients at ICU admission or shortly thereafter, contributing to a better selection of management according to the risk of death. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Muscle force and fatigue in patients with sepsis and multiorgan failure

Introduction Neuromuscular abnormalities are found frequently in sepsis and multiorgan failure (MOF). Surprisingly, however, there are no data on maximum skeletal muscle force and fatigue in these patients. Objectives To test the research hypotheses that adductor pollicis (AP) force would be lower in patients with sepsis, whereas fatigue would not differ between patients and immobilized but not infected volunteers. Design and setting Prospective study; university intensive care unit and laboratory. Patients Patients with sepsis and MOF (sequential organ failure assessment (SOFA) score >10) and healthy volunteers. Interventions Fatigue was evoked during 20 min of intermittent tetanic ulnar nerve stimulation achieving 50% of maximum AP muscle force. Measurements and results We measured evoked AP muscle force and fatigue, and compound muscle action potential (CMAP), and performed standard electrophysiological tests in 13 patients, and in 7 volunteers before and after immobilization. Maximum force (20 ± 16 vs 65 ± 19 N; p < 0.01) and CMAP (3.6 ± 2.5 vs 10 ± 2.5 mV; p < 0.05) were markedly decreased in patients; however, fatigue and ulnar nerve conduction velocity did not differ from volunteers, and a decrement of CMAP was not observed with nerve stimulation frequencies up to 40 Hz. All patients with critical illness polyneuropathy, and an additional 50% of those without, had significant muscle weakness. Conclusion Peripheral muscle force is markedly decreased in sepsis, without evidence for an increased fatigability. Muscle weakness was most likely due to a sepsis-induced myopathy and/or axonal neuropathy, and was not the result of an immobilization atrophy.     

Changes in severity and organ failure scores as prognostic factors in onco-hematological malignancy patients admitted to the ICU

Objective To determine whether severity and organ failure scores over the first 3 days in an ICU predict in-hospital mortality in onco-hematological malignancy patients.Design and setting Retrospective study in a 22-bed medical ICU.Patients 92 consecutive patients with onco-hematological malignancies including 20 hematopoietic stem cell transplantation (HSCT) patients (11 with allogenic HSCT).Measurements Simplified Acute Physiology Score (SAPS) II, Organ Dysfunction and/or Infection (ODIN) score, Logistic Organ Dysfunction System (LODS), and Sequential Organ Failure Assessment (SOFA) score were recorded on admission. The change in each score (Δ score) during the first 3 days in the ICU was calculated as follows: severity or organ failure score on day 3 minus severity or organ failure score on day 1, divided by severity or organ failure score on day 1.Results In-hospital mortality was 58%. Using multivariate analysis in-hospital mortality was predicted by all scores on day 1 and all Δ scores. Areas under the receiver operating characteristics curves were similar for SAPS II (0.78), ODIN (0.78), LODS (0.83), and SOFA (0.78) scores at day 1. They were also similar for ΔSAPS II, ΔODIN, ΔLODS, and ΔSOFA. Similar results were observed when excluding patients with allogenic HSCT.Conclusion Severity and three organ failure scores on day 1 and Δ scores perform similarly in predicting in-hospital mortality in ICU onco-hematological malignancy patients but do not predict individual outcome. Decision to admit such patients to the ICU or to forgo life-sustaining therapies should not be based on these scores.Electronic supplementary material Supplementary material is available in the online version of this article at and is accesible for authorized users.     

Outcomes and prognostic factors in patients with head and neck cancer and severe acute illnesses

Objectives To evaluate the outcomes of patients with head and neck cancer and severe acute illnesses, and to identify characteristics associated with hospital mortality. Design Cohort study. Setting Ten-bed medical–surgical oncologic intensive care unit (ICU). Patients Consecutive patients admitted to the ICU over a 68-month period. Interventions None. Measurements and results Demographic, clinical and cancer-related data were collected. Multivariate logistic regression analysis was performed to identify predictive factors of hospital mortality. One hundred and twenty-one patients aged 63.3 ± 14.7 years were enrolled in the study. The main sites of primary tumor were oral cavity (30%), larynx (25%), pharynx (14%) and thyroid (9%). The main reasons for ICU admission were sepsis (37%) and acute respiratory failure (20%). The mean SAPS II score was 49.6 ± 17.8 points, and during ICU stay 100 (83%) patients received mechanical ventilation, 70 (58%), vasopressors, and 12 (10%), dialysis. The ICU, hospital and 6-month mortality rates were 39%, 56% and 72%, respectively. A performance status ≥ 2 [odds ratio (OR) = 5.17 (95% confidence interval, CI = 1.84–14.53)], advanced cancer (TNM stage IV) [OR = 3.80 (95% CI = 1.28–11.28)], and the number of organ failures [OR=2.87 (95% CI=1.83–4.50)] were associated with increased mortality in multivariate analysis. Conclusions In conjunction with clinical judgment and taking into consideration the patient's preferences and values, the knowledge of these outcome predictors may be useful in helping physicians to identify patients who might benefit from the intensive care and to improve discussions on patients' prognosis. This work was performed at the Intensive Care Unit, Instituto Nacional de Cancer, Rio de Janeiro, Brazil. This study is original and was not previously submitted to another primary scientific journal. Preliminary data were presented as a poster at the 2005 American Head & Neck Society Annual Meeting in Boca Raton, FL, USA, and at the 9th Congress of the World Federation of Intensive and Critical Care Medicine in Buenos Aires, Argentina, 27–31 August 2005. Financial support: Institutional departmental funds Conflicts of interest: None     

Is C-reactive protein a good prognostic marker in septic patients?

Rationale  Several studies have shown that C-reactive protein (CRP) is a marker of infection. The aim of this study was to evaluate CRP as marker of prognosis outcome in septic patients and to assess the correlation of CRP with severity of sepsis. Methods  During a 14-month period, we prospectively included all patients with sepsis admitted to an intensive care unit (ICU). Patients were categorized into sepsis, severe sepsis and septic shock. Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, CRP, body temperature and white cell count (WCC) of the day of sepsis diagnosis were collected. Results  One hundred and fifty-eight consecutive septic patients (mean age 59 years, 98 men, ICU mortality 34%) were studied. The area under the receiver operating characteristics curves of APACHE II, SAPS II, SOFA, CRP, body temperature and WCC as prognostic markers of sepsis were 0.75 [95% confidence interval (CI) 0.67–0.83], 0.82 (95% CI 0.75–0.89), 0.8 (95% CI 0.72–0.88), 0.55 (95% CI 0.45–0.65), 0.48 (95% CI 0.38–0.58) and 0.46 (95% CI 0.35–0.56), respectively. In the subgroup of patients with documented sepsis we obtained similar results. The ICU mortality rate of septic patients with CRP < 10, 10–20, 20–30, 30–40 and >40 mg/dL was 20, 34, 30.8, 42.3 and 39.1%, respectively (P = 0.7). No correlation was found between CRP concentrations and severity of sepsis. Conclusions  In septic patients, CRP of the day of sepsis diagnosis is not a good marker of prognosis.     

Goal-directed fluid management reduces vasopressor and catecholamine use in cardiac surgery patients

Objective We examined whether guiding therapy by an algorithm based on optimizing the global end-diastolic volume index (GEDVI) reduces the need for vasopressor and inotropic support and helps to shorten ICU stay in cardiac surgery patients. Design and setting Single-center clinical study with a historical control group at an university hospital. Patients Forty cardiac bypass surgery patients were included prospectively and compared with a control group. Interventions In the goal-directed therapy (GDT) group hemodynamic management was guided by an algorithm based on GEDVI. Hemodynamic goals were: GEDVI above 640 ml/m², cardiac index above 2.5 l/min/m², and mean arterial pressure above 70 mmHg. The control group was treated at the discretion of the attending physician based on central venous pressure, mean arterial pressure, and clinical evaluation. Results In the GDT group duration of catecholamine and vasopressor dependence was shorter (187 ± 70 vs. 1458 ± 197 min), and fewer vasopressors (0.73 ± 0.32 vs. 6.67 ± 1.21 mg) and catecholamines (0.01 ± 0.01 vs. 0.83 ± 0.27 mg) were administered. They received more colloids (6918 ± 242 vs. 5514 ± 171 ml). Duration of mechanical ventilation (12.6 ± 3.6 vs. 15.4 ± 4.3 h) and time until achieving status of fit for ICU discharge (25 ± 13 vs. 33 ± 17 h) was shorter in the GDT group. Conclusions Guiding therapy by an algorithm based on GEDVI leads to a shortened and reduced need for vasopressors, catecholamines, mechanical ventilation, and ICU therapy in patients undergoing cardiac surgery. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Excess ICU mortality attributable to ventilator-associated pneumonia: The role of early vs late onset

Objective To determine the impact of ventilator-associated pneumonia (VAP) on ICU mortality, and whether it is related to time of onset of pneumonia. Design Prospective cohort study. Setting 16-bed medical-surgical ICU at a university-affiliated hospital. Patients and measurements From 2002 to 2003, we recorded patients receiving mechanical ventilation for > 72 h. Patients developing an infection other than VAP were excluded. Patients definitively diagnosed with VAP (n = 40) were cases and patients free of any infection acquired during ICU stay (n = 61) were controls. The VAP-attributed mortality was defined as the difference between observed mortality and predicted mortality (SAPS II) on admission. Results Mechanical ventilation was longer in VAP patients (25 ± 20 vs 11 ± 9 days; p < 0.001), as was ICU stay (33 ± 23 vs 14 ± 12 days; p < 0.001). In the non-VAP group, no difference was found between observed and predicted mortality (27.9 vs 27.4%; p > 0.2). In the VAP group, observed mortality was 45% and predicted mortality 26.5% (p < 0.001), with attributable mortality 18.5%, and relative risk (RR) 1.7 (95% CI 1.12–23.17). No difference was observed between observed and predicted mortality in early-onset VAP (27.3 vs 25.8%; p > 0.20); in late-onset VAP, observed mortality was higher (51.7 vs 26.7%; p < 0.01) with attributable mortality of 25% and an RR 1.9 (95% CI 1.26–2.63). Empiric antibiotic treatment was appropriate in 77.5% of episodes. No differences in mortality were related to treatment appropriateness. Conclusions In mechanically ventilated patients, VAP is associated with excess mortality, mostly restricted to late-onset VAP and despite appropriate antibiotic treatment.     

Renal arterial resistance in septic shock: effects of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography

Objective To determine the effects of increasing mean arterial pressure (MAP) on renal resistances assessed by Doppler ultrasonography in septic shock. Design and setting Prospective, single-center, nonrandomized, open-label trial in the surgical intensive care unit in a university teaching hospital. Patients and participants 11 patients with septic shock who required fluid resuscitation and norepinephrine to increase and maintain MAP at or above 65 mmHg. Interventions Norepinephrine was titrated in 11 patients in septic shock during three consecutive not randomized periods of 2 h to achieve a MAP at successively 65, 75, and 85 mmHg. Measurements and results At the end of each period hemodynamic parameters and renal function variables (urinary output, creatinine, clearance) were measured, and Doppler ultrasonography was performed on interlobar arteries to assess the renal resistive index. When increasing MAP from 65 to 75 mmHg, urinary output increased significantly from 76 ± 64 to 93 ± 68 ml/h and the resistive index significantly decreased from 0.75 ± 0.07 to 0.71 ± 0.06. No difference was found between 75 and 85 mmHg. Conclusions Doppler ultrasonography and resistive index measurements may help determine in each patient the optimal MAP for renal blood flow and may be a relevant end-point to titrate the hemodynamic treatment in septic shock.     

Treatment of severe acute respiratory distress syndrome: role of extracorporeal gas exchange

Objective To evaluate the effect of extracorporeal gas exchange (ECMO) on mortality of patients referred with severe acute respiratory distress syndrome (ARDS).Design and setting Prospective observational study in a university hospital ICU.Patients 150 patients with severe ARDS.Interventions Multimodal treatment with and without ECMO.Measurements and main results We treated 118 patients (78.7%) conservatively and 32 patients with ECMO. Patients in the ECMO group presented with significantly more severe disease (lung injury score 3.8 ± 0.3 vs. 3.3 ± 0.4; SOFA score 52 ± 14 vs. 43 ± 12; and SAPS score 14 ± 3.3 vs. 10 ± 3.5). Mortality in ECMO-treated patients tended to be higher than that with conservative treatment (46.9% vs. 28.8%, p = 0.059). Multivariate logistic regression analyses with backward selection excluded ECMO as predictor of mortality (p = 0.79). Independent predictors of mortality were age (odds ratio 1.044, 95% confidence interval 1.014–1.075, p = 0.004), mean pulmonary artery pressure (1.082, 1.026–1.141, p = 0.036), sequential organ failure assessment score (1.148, 1.018–1.294, p = 0.024), and days of mechanical ventilation prior to referral (1.064, 1.008–1.123, p = 0.025).Conclusion ECMO treatment does not predict mortality in patients with most severe ARDS.