Health-related quality of life outcomes with prasugrel among medically managed non-ST-segment elevation acute coronary syndrome patients: Insights from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial.

BACKGROUND: Few studies have assessed treatment effects on health-related quality of life (HRQoL) in patients with acute coronary syndrome (ACS) treated without revascularization. The TRILOGY ACS trial randomized patients with ACS to either prasugrel or clopidogrel therapy plus aspirin. Outcomes showed a complex pattern suggestive of late benefits with respect to repeat clinical events and benefits confined to patients who underwent angiography. Here, we examine the HRQoL correlates of these patterns. METHODS: HRQoL was measured at baseline and 3, 12, and 24 months or end of study (EOS) in 7243 patients aged <75 years using the EuroQol 3-level, group 5-dimension index (EQ-5D). Linear mixed effects models for repeated measures were used to examine treatment differences in HRQoL overall, stratified by angiography status, and among patients who did and did not have non-fatal events. RESULTS: No baseline differences in HRQoL were seen between patients randomized to prasugrel (n=3620) or clopidogrel (n=3623). At 24 months, remaining patients assigned to prasugrel (n=1450) vs. clopidogrel (n=1443) had higher EQ-5D index scores (86.4 vs. 84.9, P=.01). Mixed effects models found no difference in EQ-5D scores among prasugrel and clopidogrel patients overall across subgroups stratified by angiography status. However, among patients with non-fatal clinical events, patients on clopidogrel reported a larger decrement in HRQoL than patients on prasugrel (79.5±18.1 vs. 80.6±18.0; P=.02). CONCLUSIONS: Overall, there was no difference in HRQoL outcomes among patients receiving prasugrel vs. clopidogrel. However, the differential effects of the treatments among patients with non-fatal events require further investigation.

Prasugrel versus clopidogrel for acute coronary syndromes without revascularization.

BACKGROUND: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS: In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. RESULTS: At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. CONCLUSIONS: Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Resolution of polyserositis after removal of appendix mucinous cystadenoma.

Mucinous cystadenoma is a rare benign neoplasm and is usually discovered incidentally. Pleuritis and pericarditis, inflammation of the pleura and pericardium, may represent manifestations of autoimmune disorders especially in female subjects. We report a patient with polyserositis that was resolved after removal of the mucinous cystadenoma. To the best of our knowledge, this is a first report describing pleuritis and pericarditis as an initial presentation of mucinous cystadenoma of an appendix. A forty-year-old Caucasian female patient with a history of pleuritis and recurrent pericarditis was admitted to the hospital due to acute abdomen. At that time she was taking indomethacin and colchicine due to pericarditis that was controlled only with the combination of these two drugs. The patient had elevated erythrocyte sedimentation rate (ESR), increased C-reactive protein (CRP) and normocytic anemia. Immunological tests, including antinuclear antibody, anti-neutrophil cytoplasmic antibody, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies, were repeatedly negative. Emergency surgery revealed acute appendicitis with perforation and subsequent diffuse peritonitis. Histopathological examination showed acute appendicitis and mucinous cystadenoma. Following the surgery the patient did not take any drugs. Fourteen months later the patient was symptom free. Pleuritis and pericarditis in female patients are most often associated with autoimmune diseases. We assume that increased ESR and CRP with anemia detected in the patient may reflect the altered immunity that is due to mucinous cystadenoma. We believe that this report has a broader clinical impact, implying that benign tumor could alter immunity, which can lead to unusual presentation such as polyserositis.

Severe acute pancreatitis as a part of multiple dysfunction syndrome.

Acute pancreatitis is a disease with various degrees of clinical manifestations. Mild and moderate severe acute pancreatitis is an illness characterized with chemical inflammation which, in general, passes without major complications. Clinical picture of severe acute pancreatitis other side is commonly complicated with functional deterioration of other organs, and frequently has characteristics of multiple organ dysfunction or failure syndrome with or without bacterial super infection. We studied 82 patients admitted to the intensive care unit with severe acute pancreatitis, 14 died. The mortality was in statistically significant correlation with the severity of clinical condition at admission assessed by APACHE II score, and higher Ranson's and Glasgow criteria by admission. Adequate volume supplementation, on time, as well as percutaneous drainage of infected pancreas collection reduces a risk of pure outcome.

[Guidelines for the management of hyperglycaemia in hospitalised adult patients]. / Smjernice za zbrinjavanje hiperglikemije u odraslih hospitaliziranih bolesnika.

INTRODUCTION: The aim was to prepare guidelines for the management of in-hospital hyperglycaemia in adult patients in intensive care units and regular wards. CONTRIBUTORS: Working group led by two coordinators consists of repre- sentatives of professional societies within the Croatian Medical Association. EVIDENCE: These guidelines are derived from the guidelines of international professional societies. Level of evidence and strength of recommendation are evaluated according to GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. Decision making process: Working group produced Guidelines draft by a consensus. The draft has been delivered to professional societies for review. Final document is accepted by all included societies. CONCLUSION: Hyperglycaemia is a frequent, serious and demanding complication in hospitalized patients. Results of published studies suggest that its regulation decreases morbidity and mortality. Implementation of locally developed standardized protocols promoting basal-bolus insulin regimen is regarded as the most important measure for management of hyperglycaemia in hospital. Present guidelines are a set of practical, rational and feasible recommendations and suggestions.

Prior statin therapy is associated with milder course and better outcome in acute pancreatitis--a cohort study.

BACKGROUND: Statin treatment was shown to be associated with improved outcomes in several inflammatory conditions. We wanted to evaluate the effects of statin therapy on the course and outcome of acute pancreatitis (AP). METHODS: A prospective cohort study included patients with acute pancreatitis divided into two groups according to statin use prior to hospitalization. Age, sex, etiology of AP, Ranson's score, APACHE II score and maximal CRP were recorded. Outcome measures were hospital length of stay and mortality. Matching of patients for matched analyses was done using individual matching and propensity score matching using variables a priori associated with course and outcome of acute pancreatitis. RESULTS: Inclusion criteria were met for 1062 patients of whom 92 were taking statins. Statin users were older and had higher body mass indexes. Severe disease was more common in the no-statin group than in statin group (20.6% vs. 8.7% respectively). All severity markers were also higher in the no-statin group. All cause mortality was not different, while cardiovascular mortality was higher in the statin group in the cohort analysis. After matching by either method, the severity of disease was greater for the patients without statins treatment. Pancreatitis related mortality was higher in the no-statin group after matching. Among patients who developed severe AP, statin users showed lower Ranson's and APACHE II scores and lower maximal CRP. CONCLUSIONS: Prior statin treatment significantly reduces morbidity and mortality in acute pancreatitis. Further studies are needed to evaluate possible therapeutic use of statins in acute pancreatitis.

Extramedullary plasmacytoma imitating neoplasm of the gallbladder fossa after cholecystectomy.

Extramedullary plasmacytomas are plasma cell tumors that arise outside of the bone marrow. They account for approximately 3% of plasma cell neoplasms and are most frequently located in the head and neck region. Five months after undergoing cholecystectomy, a 69-year-old patient presented with the pain under the right costal margin and a 12 kg weight loss. Computed tomography of the abdomen demonstrated irregular, vascular mass in the gallbladder fossa that dents towards the duodenum and the pylorus and lowers caudally to the hepatic flexure. His laboratory tests indicated normocytic anemia and showed elevated sedimentation rate. During operative procedure, a tumorous mass in the gallbladder fossa was found, inseparable of the peritoneum of the hepatoduodenal ligament and the IVb liver segment. Histopathological examination and immunohistochemical staining determined the diagnosis of the plasmacytoma. Total resection of the tumor was achieved and after 24-month follow-up patient showed no signs of local recurrence or dissemination of the disease.

A prospective observational study of the relationship of critical illness associated hyperglycaemia in medical ICU patients and subsequent development of type 2 diabetes.

INTRODUCTION: Critical illness is commonly complicated by hyperglycaemia caused by mediators of stress and inflammation. Severity of disease is the main risk factor for development of hyperglycaemia, but not all severely ill develop hyperglycemia and some do even in mild disease. We hypothesised that acute disease only exposes a latent disturbance of glucose metabolism which puts those patients at higher risk for developing diabetes. METHODS: Medical patients with no history of impaired glucose metabolism or other endocrine disorder admitted to an intensive care unit between July 1998 and June 2004 were considered for inclusion. Glucose was measured at least two times a day, and patients were divided into the hyperglycaemia group (glucose ≥7.8 mmol/l) and normoglycaemia group. An oral glucose tolerance test was performed within six weeks after discharge to disclose patients with unknown diabetes or pre-diabetes who were excluded. Patients treated with corticosteroids and those terminally ill were also excluded from the follow-up which lasted for a minimum of five years with annual oral glucose tolerance tests. RESULTS: A five-year follow-up was completed for 398 patients in the normoglycaemia group, of which 14 (3.5%) developed type 2 diabetes. In the hyperglycaemia group 193 patients finished follow-up and 33 (17.1%) developed type 2 diabetes. The relative risk for type 2 diabetes during five years after the acute illness was 5.6 (95% confidence interval (CI) 3.1 to 10.2). CONCLUSIONS: Patients with hyperglycaemia during acute illness who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes. They should, therefore, be followed-up, in order to be timely diagnosed and treated.

Thrombotic thrombocytopenic purpura--the role of ADAMTS13 assay in clinical practice.

Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by disseminated thrombotic occlusions of the microcirculation. Identification of ADAMTS13 protease and its place in the pathophysiology of TTP led to better understanding of the disease and better survival for the diseased. Here we show a case report of a patient that had a normal ADAMTS13protease activity and an unusual clinical presentation and utilize that case to highlight how the absence of a severe ADAMTS13 protease deficiency does not preclude a diagnosis of TTP and how early initiation and continuation of plasma exchange therapy can lead to a positive outcome, even in a severely ill patient. Even though ADAMTS13 protease determination has no immediate influence on the decision whether or not to start the plasma exchange therapy, it has great impact on future management of the patient and should be determined whenever possible.

Obese patients in medical intensive care unit: influence of counseling on weight loss and cardiovascular parameters.

A case series of 12 obese patients admitted to medical intensive care unit (ICU) due to life-threatening diseases and the influence of weight loss on cardiovascular parameters is presented. We assessed body weight, body mass index (BMI), blood pressure, pulse, and laboratory values on admission. At discharge from ICU patients were counseled on how to lose weight. They were examined one and six months later. Statistically significant (p < 0.05) decrease of body weight (median at the beginning of a treatment 134 kg, after six months 127.5 kg), BMI (median 41.5 kg/m2 at the beginning of a treatment; 38.9 kg/m2 after six months), systolic blood pressure (medians 145 mmHg and 130 mmHg), diastolic blood pressure (medians 95 mmHg and 85 mmHg) and pulse (medians 104 beats per minute, 78 beats per minute) was found. The reduction of the waist circumference was not significant. One patient died due to severe acute pancreatitis. Patients reported feeling much better after losing weight.

[Possibilities of prevention of nephrotoxicity in intensive care unit]. / Mogucnosti prevencije nefrotoksicnog ucinka u intenzivnoj jedinici.

Different nephrotoxic drugs (antibiotic, antifungal, chemotherapeutic, NSAR, cyclosporine) as well as radio contrasts are mainly responsible for impairment of the renal funciton. Some patient populations, like diabetics, older patients and dehydrated patients are in additional risk for kidney failure. The challenge for protection of kidney function is complex, but it is possible in different clinical conditions to influence nephrotoxicity. The prevention of acute renal failure is very important, because this complication is according to many publications a significant risk for mortality. The administration of N acetilcystein, bicarbonate infusion, magnesium infusion, calcium channel blockers are promising strategies. It is very important to stress adequate rehydratation of every single patient, but some patient populations like diabetics, older patients and dehydrated patients are in special risk for nefrotoxicity. Because today radio contrast media are also important reason for nephrotoxicity, the use of low and iso-osmolar contrasts provides additional possibilities for prevention of potential nephrotoxicity.

[Hypothermia after cardiac arrest--underused method that saves lives]. / Hipotermija nakon kardijalnog aresta--premalo upotrebljavana metoda koja spasava zivote.

Cardiorespiratory arrest causes ischemia and lesion of all organ systems, but the central nervous system is the most vulnerable. It is known that only few minutes of hypoperfusion and ischemia can cause irreversible damage to the brain which is the major frustration of reanimatology. Results of clinical trials suggest positive effects of hypothermia on survival and neurological recovery which led to including this method to Guidelines for resuscitation as a recommended standard method in post-resuscitation period for patients who have not regained consciousness. Methods for induction and maintenance of hypothermia are numerous and various, basically divided into invasive and non-invasive, each with its own advantages and disadvantages which are described in this paper. Despite recognised positive effects of mild therapeutic hypothermia after resuscitation from cardiac arrest, the method is not fully implemented as a standard method in post-resuscitation period.

Impact of remote ischemic preconditioning preceding coronary artery bypass grafting on inducing neuroprotection.

BACKGROUND: Neurological complications after coronary artery bypass grafting (CABG) reduce quality of life, increase mortality, and inflate resource utilization. The risk of postoperative neurological complications parallels the increasing risk burden of the contemporary patient population. We evaluated the efficacy of remote ischemic preconditioning (RIPC) on inducing neuroprotection. METHODS: Seventy patients undergoing first-time CABG were randomly assigned to RIPC or a sham procedure. Structural brain magnetic resonance imaging (MRI) was complemented with functional connectivity MRI to gain a whole-brain global connectivity analysis. Paired neurocognitive and MRI data were acquired pre- and postoperatively. The primary end point was a composite of new ischemic brain lesions and neurocognitive impairment. Secondary end points included brain connectivity profiles, pooled ischemic volumes, and individual components of the primary outcome. The Shapiro-Wilk test was used to determine whether a data set followed a normal distribution. The Fisher exact test was used to calculate the measures of association for categorical variables, whereas continuous data were tested with either the Mann-Whitney U test or the Student t test. RESULTS: There was no between-group difference in the incidence of the primary end point (9 [27%] in the RIPC group vs 8 [24%] in the control group, odds ratio, 1.17 [95% confidence interval, 0.34-4.06]; P = 1.0). Although RIPC did not reduce the incidence of brain ischemia (8/33 [24%] vs 7/33 [21%]; P = 1.0), the pooled ischemic volume was lower in the RIPC group (157 [interquartile range, 125-231] vs 777 [interquartile range, 564-965] mm3; P = .004). Postoperative neurocognition was marginally superior in the RIPC group as evidenced by a lower absolute number of abnormal neurocognitive tests in the RIPC group (7/99 [7%] vs 16/99 [16%]; odds ratio, 0.40 [95% confidence interval, 0.14-1.09]; P = .074). Robust reductions of functional connectivity profiles for the associative thalamus were documented in both groups, irrespective of RIPC (RIPC group, t = 3.31; P < .01; and the control group, t = 3.52; P < .01). CONCLUSIONS: Silent brain ischemia occurs frequently after CABG. RIPC did not reduce the incidence of the primary outcome. However, RIPC significantly reduced the pooled volume of ischemic brain lesions. Surgery adversely affected global brain connectivity, with RIPC conferring no demonstrable protection. The association of RIPC with superior neurocognitive test scores failed to cross the threshold for significance.

Fatal toxic epidermal necrolysis and severe granulocytopenia following therapy with cefuroxime.

Toxic epidermal necrolysis (TEN) is one of the most threatening adverse reactions to various drugs. No case of concomitant occurrence TEN and severe granulocytopenia following the treatment with cefuroxime has been reported to date. Herein we present a case of TEN that developed eighteen days of the initiation of cefuroxime axetil therapy for urinary tract infection in a 73-year-old woman with chronic renal failure and no previous history of allergic diathesis. The condition was associated with severe granulocytopenia and followed by gastrointestinal hemorrhage, severe sepsis and multiple organ failure syndrome development. Despite intensive medical treatment the patient died. The present report underlines the potential of cefuroxime to simultaneously induce life threatening adverse effects such as TEN and severe granulocytopenia. Further on, because the patient was also taking furosemide for chronic renal failure, the possible unfavorable interactions between the two drugs could be hypothesized. Therefore, awareness of the possible drug interaction is necessary, especially when given in conditions of their altered pharmacokinetics as in case of chronic renal failure.

HbA1c is outcome predictor in diabetic patients with sepsis.

We have investigated predictive value of HbA1c for hospital mortality and length of stay (LOS) in patients with type 2 diabetes admitted because of sepsis. A prospective observational study was implemented in a university hospital, 286 patients with type 2 diabetes admitted with sepsis were included. Leukocyte count, CRP, admission plasma glucose, APACHE II and SOFA score were noted at admission, HbA1c was measured on the first day following admission. Hospital mortality and hospital length of stay (LOS) were the outcome measures. Admission HbA1c was significantly lower in surviving patients than in non-survivors (median 8.2% versus 9.75%, respectively; P<0.001). There was a significant correlation between admission HbA1c and hospital LOS of surviving patients (r=0.29; P<0.001). Logistic regression showed that HbA1c is an independent predictor of hospital mortality (odds ratio 1.36), together with female sex (OR 2.24), APACHE II score (OR 1.08) and SOFA score (OR 1.28). Multiple regression showed that HbA1c and APACHE II score are independently related to hospital LOS. According to our results, HbA1c is an independent predictive factor for hospital mortality and hospital LOS of diabetic patients with sepsis.

[Anorexia nervosa: a life threatening condition]. / Anorexia nervosa: stanje zivotne ugrozenosti.

Anorexia nervosa is an eating disorder which, in case of life threating complications, requires admission to the intensive care unit. Our experience shows that danger for these patients does not always stop upon the admission to the intensive care unit. Four young, vitally endangered patients with anorexia nervosa were described. Three of them had severe acute inflammation (2 pneumonias and peritonitis) and severe electrolyte imbalance which in one case resulted in cardiorespiratory arrest and the need for resuscitation. One of them died despite all measures taken in sepsis with multiple organ dysfunction syndrome. Prolonged electrolyte disturbances in anorexia nervosa, catabolism and insufficient immunity are main factors for developing an acute inflammation, as well as some other complications such as cardiorespiratory failure, nosocomial infection, and sepsis with multiple organ failure. Weak and totally exhausted body can not adapt in MODS and sepsis, so our recommendation is urgent admission to the hospital before it is too late.

Opening pressures and atelectrauma in acute respiratory distress syndrome.

PURPOSE: Open lung strategy during ARDS aims to decrease the ventilator-induced lung injury by minimizing the atelectrauma and stress/strain maldistribution. We aim to assess how much of the lung is opened and kept open within the limits of mechanical ventilation considered safe (i.e., plateau pressure 30 cmH2O, PEEP 15 cmH2O). METHODS: Prospective study from two university hospitals. Thirty-three ARDS patients (5 mild, 10 moderate, 9 severe without extracorporeal support, ECMO, and 9 severe with it) underwent two low-dose end-expiratory CT scans at PEEP 5 and 15 cmH2O and four end-inspiratory CT scans (from 19 to 40 cmH2O). Recruitment was defined as the fraction of lung tissue which regained inflation. The atelectrauma was estimated as the difference between the intratidal tissue collapse at 5 and 15 cmH2O PEEP. Lung ventilation inhomogeneities were estimated as the ratio of inflation between neighboring lung units. RESULTS: The lung tissue which is opened between 30 and 45 cmH2O (i.e., always closed at plateau 30 cmH2O) was 10 ± 29, 54 ± 86, 162 ± 92, and 185 ± 134 g in mild, moderate, and severe ARDS without and with ECMO, respectively (p < 0.05 mild versus severe without or with ECMO). The intratidal collapses were similar at PEEP 5 and 15 cmH2O (63 ± 26 vs 39 ± 32 g in mild ARDS, p = 0.23; 92 ± 53 vs 78 ± 142 g in moderate ARDS, p = 0.76; 110 ± 91 vs 89 ± 93, p = 0.57 in severe ARDS without ECMO; 135 ± 100 vs 104 ± 80, p = 0.32 in severe ARDS with ECMO). Increasing the applied airway pressure up to 45 cmH2O decreased the lung inhomogeneity slightly (but significantly) in mild and moderate ARDS, but not in severe ARDS. CONCLUSIONS: Data show that the prerequisites of the open lung strategy are not satisfied using PEEP up to 15 cmH2O and plateau pressure up to 30 cmH2O. For an effective open lung strategy, higher pressures are required. Therefore, risks of atelectrauma must be weighted versus risks of volutrauma. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01670747 ( www.clinicaltrials.gov ).

Randomized, multicenter trial of lateral Trendelenburg versus semirecumbent body position for the prevention of ventilator-associated pneumonia.

PURPOSE: The lateral Trendelenburg position (LTP) may hinder the primary pathophysiologic mechanism of ventilator-associated pneumonia (VAP). We investigated whether placing patients in the LTP would reduce the incidence of VAP in comparison with the semirecumbent position (SRP). METHODS: This was a randomized, multicenter, controlled study in invasively ventilated critically ill patients. Two preplanned interim analyses were performed. Patients were randomized to be placed in the LTP or the SRP. The primary outcome, assessed by intention-to-treat analysis, was incidence of microbiologically confirmed VAP. Major secondary outcomes included mortality, duration of mechanical ventilation, and intensive care unit length of stay. RESULTS: At the second interim analysis, the trial was stopped because of low incidence of VAP, lack of benefit in secondary outcomes, and occurrence of adverse events. A total of 194 patients in the LTP group and 201 in the SRP group were included in the final intention-to-treat analysis. The incidence of microbiologically confirmed VAP was 0.5% (1/194) and 4.0% (8/201) in LTP and SRP patients, respectively (relative risk 0.13, 95% CI 0.02-1.03, p = 0.04). The 28-day mortality was 30.9% (60/194) and 26.4% (53/201) in LTP and SRP patients, respectively (relative risk 1.17, 95% CI 0.86-1.60, p = 0.32). Likewise, no differences were found in other secondary outcomes. Six serious adverse events were described in LTP patients (p = 0.01 vs. SRP). CONCLUSIONS: The LTP slightly decreased the incidence of microbiologically confirmed VAP. Nevertheless, given the early termination of the trial, the low incidence of VAP, and the adverse events associated with the LTP, the study failed to prove any significant benefit. Further clinical investigation is strongly warranted; however, at this time, the LTP cannot be recommended as a VAP preventive measure. CLINICALTRIALS. GOV IDENTIFIER: NCT01138540.

Sepsis syndrome in Croatian intensive care units: piloting a national comparative clinical database.

AIM: To assess the incidence of sepsis in selected intensive care units (ICUs) in Croatia, isolates from blood cultures, and sepsis outcomes, and to compare the results with those from other European countries. METHODS: In the pilot phase of the national comparative clinical database project, we included 24 ICUs--general, specialized, neonatal, pediatric, and adult--18 from university hospitals, 3 from county hospitals, and 4 from city hospitals. By retrospective chart review, trained data collectors abstracted the data on the case mix, management strategies, and outcomes in patients consecutively admitted to ICUs. Central validation for incomplete, illogical, or inconsistent values is regularly performed to improve accurateness. RESULTS: Of 5293 patients treated in 24 ICUs from November 1, 2004, to October 31, 2005, 456 (8.6%) were treated for sepsis syndrome or severe sepsis. The most common isolates from positive blood cultures were Esherichia coli (11.6%), Pseudomonas species (9.9%), and methicillin-resistant Staphylococcus aureus (9.3%). With the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 10.0 and Sequential Organ Failure Assessment (SOFA) score of 2.4, the overall mortality for sepsis syndrome, severe sepsis, and septic shock was 29%, 35%, and 34%, respectively. When compared to university hospitals and county hospitals, city hospitals with the smallest gravitating population had significantly lower APACHE II and SOFA scores, but significantly higher mortality. CONCLUSIONS: Overall mortality of patients with sepsis syndrome in Croatian ICUs was high, but outcomes of their treatment were comparable with those in other European countries. Better education in triage and treatment strategies is needed, including better implementation of Surviving Sepsis Campaign guidelines.