The use of hypnotic communication in PICC placement: randomized controlled trial study.

Every time a patient undergoes a medical procedure, unpredicted personal stress occurs. According to the available literature, the hypnotic communication technique has been used to reduce stress and pain during several major invasive procedures. The primary goal of this study was to compare the effectiveness of hypnotic communication combined with buffered Lidocaine, versus buffered Lidocaine alone, on patients' negative emotions while undergoing Peripherally Inserted Central Venous Catheter (PICC) placement. Secondary aims were evaluating patients' pain, satisfaction, and procedure timing and costs. A randomized controlled trial was conducted in an Italian Hospital involving patients who needed a PICC, with any disease or condition, aged over 18, cognitively oriented, able to hear, and willing to give consent. Emotional assessment was performed using the Emotion Thermometer Tool. Sixty-seven subjects were enrolled: 17 refused to participate, and 25 were randomly assigned to each group. The results showed a statistically significant higher decline in the total Emotion Thermometer Tool score for the experimental group using hypnotic communication. A significant mean reduction in anger and depression was also observed, while both groups reported low levels of perceived pain. Hypnotic communication appears to be a successful method for reducing emotional stress during PICC placement. However, further research is needed to determine the relationship between hypnotic communication, emotional distress, and pain perception in patients undergoing central vascular catheter insertion.

Heparin dosage, level, and resistance in SARS-CoV2 infected patients in intensive care unit.

INTRODUCTION: Patients with COVID-19 frequently exhibit a hypercoagulable state with high thrombotic risk, particularly those admitted to intensive care units (ICU). Thromboprophylaxis is mandatory in these patients; nevertheless, thrombosis still occurs in many cases. Thus, the problem of assessing an adequate level of anticoagulation in ICU patients becomes evident during the COVID-19 pandemic. The aim of this study was to evaluate the heparin resistance and the efficacy of heparin monitoring using an anti-Xa activity assay. METHODS: Thirty-seven heparin-treated patients admitted to ICU for SARS-CoV-2 pneumonia were retrospectively studied for antifactor Xa activity (anti-Xa), activated partial thromboplastin time (APTT), Antithrombin, Fibrinogen, D-Dimer, Factor VIII, von Willebrand Factor, and the total daily amount of heparin administered. The correlation between APTT and anti-Xa was evaluated for unfractionated heparins (UFH). The correlations between the daily dose of UFH or the dosage expressed as IU/kg b.w. for low molecular weight heparin (LMWH) and anti-Xa were also evaluated. RESULTS: Twenty-one patients received calcium heparin, 8 sodium heparin, and 8 LMWH. A moderate correlation was found between APTT and anti-Xa for UFH. APTT did not correlate with coagulation parameters. 62% of UFH and 75% of LMWH treated patients were under the therapeutic range. About 75% of patients could be considered resistant to heparin. CONCLUSIONS: SARS-COV2 pneumonia patients in ICU have frequently heparin resistance. Anti-Xa seems a more reliable method to monitor heparin treatment than APTT in acute patients, also because the assay is insensitive to the increased levels of fibrinogen, FVIII, and LAC that are common during the COVID-19 inflammatory state.

Iatrogenic anaemia and transfusion thresholds in ICU patients with COVID-19 disease at a tertiary care hospital.

BACKGROUND: Patients with severe COVID-19 disease frequently develop anaemia as the result of multiple mechanisms and often receive transfusions. The aims of this study were to assess the impact of repeated blood samplings on patients' anaemic state using standard-volume tubes, in comparison with the hypothetical use of low-volume tubes and to evaluate the transfusion policy adopted. STUDY DESIGN AND METHODS: Transfusion data of mechanically ventilated non-bleeding patients with COVID-19 disease hospitalized in ICU for a minimum of 20 days were recorded. The total volume of blood drawn for samplings with standard-volume tubes and the corresponding red blood cell mass (RBCM) removed during hospitalization for each patient were calculated and compared with the hypothetical use of low-volume tubes. RESULTS: Twenty-four patients fulfilled the inclusion criteria. Ten patients were anaemic at ICU admission (41.7 %). Overall, 6658 sampling tubes were employed, for a total of 16,786 mL of blood. The median RBCM subtracted by blood samplings per patient accounted for about one third of the total patients' RBCM decrease until discharge. The use of low-volume tubes would have led to a median saving of about one third of the drawn RBCM. Eleven patients were transfused (45.8 %) at a mean Hb value of 7.7 (± 0.5) g/dL. CONCLUSION: The amount of blood drawn for sampling has a significant role in the development of anaemia and the use of low-volume tubes could minimize the problem. Large high-powered studies are warranted to assess the more appropriate transfusion thresholds in non-bleeding critically ill patients with COVID-19 disease.

Noninvasive Ventilatory Support of Patients with COVID-19 outside the Intensive Care Units (WARd-COVID).

Rationale: Treatment with noninvasive ventilation (NIV) in coronavirus disease (COVID-19) is frequent. Shortage of intensive care unit (ICU) beds led clinicians to deliver NIV also outside ICUs. Data about the use of NIV in COVID-19 is limited.Objectives: To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death).Methods: In this prospective, single-day observational study, we enrolled adult patients with COVID-19 who were treated with NIV outside the ICU from 31 hospitals in Lombardy, Italy.Results: We collected data on demographic and clinical characteristics, ventilatory management, and patient outcomes. Of 8,753 patients with COVID-19 present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. A majority of patients (778/909; 85%) patients were treated with continuous positive airway pressure (CPAP), which was delivered by helmet in 617 (68%) patients. NIV failed in 300 patients (37.6%), whereas 498 (62.4%) patients were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with an arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio <150 mm Hg. Higher C-reactive protein and lower PaO2/FiO2 and platelet counts were independently associated with increased risk of NIV failure.Conclusions: The use of NIV outside the ICUs was common in COVID-19, with a predominant use of helmet CPAP, with a rate of success >60% and close to 75% in full-treatment patients. C-reactive protein, PaO2/FiO2, and platelet counts were independently associated with increased risk of NIV failure.Clinical trial registered with ClinicalTrials.gov (NCT04382235).

PROSAFE: a European endeavor to improve quality of critical care medicine in seven countries.

BACKGROUND: Long-lasting shared research databases are an important source of epidemiological information and can promote comparison between different healthcare services. Here we present PROSAFE, an advanced international research network in intensive care medicine, with the focus on assessing and improving the quality of care. The project involved 343 ICUs in seven countries. All patients admitted to the ICU were eligible for data collection. METHODS: The PROSAFE network collected data using the same electronic case report form translated into the corresponding languages. A complex, multidimensional validation system was implemented to ensure maximum data quality. Individual and aggregate reports by country, region, and ICU type were prepared annually. A web-based data-sharing system allowed participants to autonomously perform different analyses on both own data and the entire database. RESULTS: The final analysis was restricted to 262 general ICUs and 432,223 adult patients, mostly admitted to Italian units, where a research network had been active since 1991. Organization of critical care medicine in the seven countries was relatively similar, in terms of staffing, case mix and procedures, suggesting a common understanding of the role of critical care medicine. Conversely, ICU equipment differed, and patient outcomes showed wide variations among countries. CONCLUSIONS: PROSAFE is a permanent, stable, open access, multilingual database for clinical benchmarking, ICU self-evaluation and research within and across countries, which offers a unique opportunity to improve the quality of critical care. Its entry into routine clinical practice on a voluntary basis is testimony to the success and viability of the endeavor.

Management of critically ill patients with COVID-19: suggestions and instructions from the coordination of intensive care units of Lombardy.

With 63,098 confirmed cases on 17 April 2020 and 11,384 deaths, Lombardy has been the most affected region in Italy by coronavirus disease 2019 (COVID-19). To cope with this emergency, the COVID-19 Lombardy intensive care units (ICU) network was created. The network identified the need of defining a list of clinical recommendations to standardize treatment of patients with COVID-19 admitted to Intensive Care Unit (ICU). Three core topics were identified: 1) rational use of intensive care resources; 2) ventilation strategies; 3) non-ventilatory interventions. Identification of patients who may benefit from ICU treatment is challenging. Clinicians should consider baseline performance and frailty status and they should adopt disease-specific staging tools. Continuous positive airway pressure, mainly delivered through a helmet as elective method, should be considered as initial treatment for all patients with respiratory failure associated with COVID-19. In case of persisting dyspnea and/or desaturation despite 4-6 hours of noninvasive ventilation, endotracheal intubation and invasive mechanical ventilation should be considered. In the early phase, muscle relaxant use and volume-controlled ventilation is recommended. Prone position should be performed in patients with PaO2/FiO2≤100 mmHg. For patients admitted to ICU with COVID-19 interstitial pneumonia, we do not recommend empiric antibiotic therapy for community-acquired pneumonia. Consultation of an infectious disease specialist is suggested before start of any antiviral therapy. In conclusion, the COVID-19 Lombardy ICU Network identified a list of best practice statements supported by the available evidence and clinical experience or identified as panel members expert opinions for the management of critically ill patients with COVID-19.

Acute Lower Limb Ischemia as Clinical Presentation of COVID-19 Infection.

Novel 2019 coronavirus (COVID-19) infection usually causes a respiratory disease that may vary in severity from mild symptoms to severe pneumonia with multiple organ failure. Coagulation abnormalities are frequent, and reports suggest that COVID-19 may predispose to venous and arterial thrombotic complications. We report a case of acute lower limb ischemia and resistance to heparin as the onset of COVID-19 disease, preceding the development of respiratory failure. This case highlights that the shift of coagulation profile toward hypercoagulability was associated with the acute ischemic event and influenced the therapy.

Decrease of Non-Classical and Intermediate Monocyte Subsets in Severe Acute SARS-CoV-2 Infection.

In patients with severe SARS-CoV-2 infection, the development of cytokine storm induces extensive lung damage, and monocytes play a role in this pathological process. Non-classical (NC) and intermediate (INT) monocytes are known to be involved during viral and bacterial infections. In this study, 30 patients with different manifestations of acute SARS-CoV-2 infection were investigated with a flow cytometric study of NC, INT, and classical (CL) monocytes. Significantly reduced NC and INT monocytes and a downregulated HLA-DR were found in acute patients with severe SARS-CoV-2 symptoms. Conversely in patients with moderate symptoms NC and INT monocytes and CD11b expression were increased. © 2020 International Society for Advancement of Cytometry.

Epidural analgesia vs systemic opioids in patients undergoing laparoscopic colorectal surgery.

PURPOSE: A well-controlled pain is one of the most important targets of enhanced recovery after surgery (ERAS) protocols. Recent studies questioned the role of TEA (thoracic epidural analgesia) in support of less invasive techniques, in particular in laparoscopic mini-invasive surgery. The aim of this study is to compare patients undergoing laparoscopic mini-invasive colorectal surgery and receiving different analgesic techniques. METHODS: Prospectively collected data entered in the electronic registry of POIS (Perioperative Italian Society) specifically designed for ERAS were reviewed. Patients undergoing colorectal laparoscopic surgery were divided in two groups according to TEA or parenteral opioid administration. In comparing TEA and opioid groups, propensity score weights were obtained. Postoperative pain control and time to readiness for discharge (TRD) were considered as primary endpoints of the study. Secondary endpoints were postoperative morbidity, PONV (postoperative nausea and vomiting), hours of mobilization, length of hospital stay (LOS), timing of fluid and solid re-assumption, and recovery of bowel function. RESULTS: Fourteen Italian hospitals reported data on 560 patients (283 TEA, 277 opioid group). Patients of the opioid group were able to mobilize for a longer period than TEA group patients but presented a higher incidence of PONV. Pain intensity and TRD were similar in both groups. LOS was significantly reduced in TEA patients; also, this result was clinically irrelevant (5.7 ± 3.21 days TEA group vs 5.8 ± 2.92 opioid group). CONCLUSION: In patients undergoing laparoscopic colorectal surgery, TEA was not associated to a better pain control or to an improvement in postoperative outcome compared with opioid administration.

Identification of core items in the enhanced recovery pathway.

BACKGROUND & AIMS: The Enhanced Recovery After Surgery (ERAS) pathway represents an optimal approach in patients undergoing colorectal surgery but complexity in implementing its items could limit its application. The aim of this study is to identify possible core items within an ERAS pathway following elective colorectal resection. METHODS: This is a retrospective review of data prospectively collected between January 2014 and September 2015 by 14 Italian Hospitals in an electronic registry dedicated to an ERAS protocol. 722 patients undergoing elective colorectal surgery within an ERAS protocol have been included in the study. Adherence to ERAS items was assessed in all patients. A secondary analysis was restricted to pre- and intraoperative ERAS items. Time to readiness for discharge (TRD) was the primary endpoint of the study. Postoperative overall morbidity was the secondary endpoint. RESULTS: Multivariate analyses showed that active intraoperative warming (p = 0.008), early stop of intravenous fluids (p = 0.0001), and early removal of urinary catheter (p = 0.0001) were associated to a shorter TRD, while early stop of intravenous fluids (p < 0.001) also reduced morbidity. When the analysis was restricted to pre- and intraoperative items, removal of NGT at the end of surgery had an independent role to shorten TRD (p < 0.001) and to reduce overall morbidity (p = 0.019), while the absence of oral bowel preparation reduced postoperative overall morbidity (p = 0.021). CONCLUSIONS: In implementing an ERAS pathway, hospitals could initially focus on active intraoperative warming, early stop of intravenous fluids, early removal of urinary catheter, removal of NGT at the end of surgery, and absence of oral bowel preparation, keeping on continuous effort to apply the complete ERAS protocol.

Enhanced recovery pathway in elderly patients undergoing colorectal surgery: is there an effect of increasing ages? Results from the perioperative Italian Society Registry.

Previous studies reported that enhanced recovery pathway (ERP) is safe in elderly who did not require a specifically tailored protocol. In previous studies, elderly have been considered as a homogeneous cohort and the cut-off value to identify them was different. The aim of the present study is to assess the compliance to ERP and its impact on postoperative outcome in three subgroups of elderly patients with increasing ages. Prospectively collected data entered in an electronic Italian registry specifically designed for ERP were reviewed. 315 elderly patients undergoing elective colorectal resection were divided into three groups. Group 1: 71-75 years (n = 105), Group 2: 76-80 years (n = 117), Group 3: over 80 years (n = 93). Primary endpoints of the study were adherence to ERP and time to readiness for discharge (TRD). Compliance to ERP was similar in the three groups. No difference among groups was found for mortality, overall morbidity, major complications, reoperation rate and readmission rate. Median TRD and length of hospital stay (LOS) were progressively longer with increasing age (p = 0.018 and p = 0.078, respectively). Increasing age did not impact on adherence to ERP and postoperative morbidity, but delayed both TRD and LOS.

The prognostic importance of chronic end-stage diseases in geriatric patients admitted to 163 Italian ICUs.

BACKGROUND: The number of elderly patients undergoing major surgical interventions and then needing admission to intensive care unit (ICU) grows steadily. We investigated this issue in a cohort of 232,278 patients admitted in five years (2011-2015) to 163 Italian general ICUs. METHODS: Surgical patients older than 75 registered in the GiViTI MargheritaPROSAFE project were analyzed. The impact on hospital mortality of important chronic conditions (severe COPD, NYHA class IV, dementia, end-stage renal disease, cirrhosis with portal hypertension) was investigated with two prognostic models developed yearly on patients staying in the ICU less or more than 24 hours. RESULTS: 44,551 elderly patients (19.2%) underwent emergency (47.3%) or elective surgery (52.7%). At least one severe comorbidity was present in 14.6% of them, yielding a higher hospital mortality (32.4%, vs. 21.1% without severe comorbidity). In the models for patients staying in the ICU 24 hours or more, cirrhosis, NYHA class IV, and severe COPD were constant independent predictors of death (adjusted odds ratios [ORs] range 1.67-1.97, 1.54-1.91, and 1.34-1.50, respectively), while dementia was statistically significant in four out of five models (adjusted ORs 1.23-1.28). End-stage renal disease, instead, never resulted to be an independent prognostic factor. For patients staying in the ICU less than 24 hours, chronic comorbidities were only occasionally independent predictors of death. CONCLUSIONS: Our study confirms that elderly surgical patients represent a relevant part of all ICUs admissions. About one of seven bear at least one severe chronic comorbidity, that, excluding end-stage renal disease, are all strong independent predictors of hospital death.

The Domains of Human Nutrition: The Importance of Nutrition Education in Academia and Medical Schools.

Human nutrition encompasses an extremely broad range of medical, social, commercial, and ethical domains and thus represents a wide, interdisciplinary scientific and cultural discipline. The high prevalence of both disease-related malnutrition and overweight/obesity represents an important risk factor for disease burden and mortality worldwide. It is the opinion of Federation of the Italian Nutrition Societies (FeSIN) that these two sides of the same coin, with their sociocultural background, are related to a low "nutritional culture" secondary, at least in part, to an insufficient academic training for health-care professionals (HCPs). Therefore, FeSIN created a study group, composed of delegates of all the federated societies and representing the different HCPs involved in human nutrition, with the aim of identifying and defining the domains of human nutrition in the attempt to more clearly define the cultural identity of human nutrition in an academically and professionally oriented perspective and to report the conclusions in a position paper. Three main domains of human nutrition, namely, basic nutrition, applied nutrition, and clinical nutrition, were identified. FeSIN has examined the areas of knowledge pertinent to human nutrition. Thirty-two items were identified, attributed to one or more of the three domains and ranked considering their diverse importance for academic training in the different domains of human nutrition. Finally, the study group proposed the attribution of the different areas of knowledge to the degree courses where training in human nutrition is deemed necessary (e.g., schools of medicine, biology, nursing, etc.). It is conceivable that, in the near future, a better integration of the professionals involved in the field of human nutrition will eventually occur based on the progressive consolidation of knowledge, competence, and skills in the different areas and domains of this discipline.

Enhanced Recovery Program in High-Risk Patients Undergoing Colorectal Surgery: Results from the PeriOperative Italian Society Registry.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways represent the optimal approach for patients undergoing colorectal surgery. Elderly or low physical status patients have been often excluded from ERAS pathways because considered at high risk. The aim of this study is to assess the adherence to ERAS protocol and its impact on short-term postoperative outcome in patients with different surgical risk undergoing elective colorectal resection. METHODS: Prospectively collected data entered in an electronic Italian registry specifically designed for ERAS were reviewed. Patients were divided into four groups according to age (70-year-old cutoff) and preoperative physical status as measured by the ASA grade (I-II vs. III-IV). Adherence to 18 ERAS elements and postoperative outcomes were compared between groups. Regression analysis was used to identify independent factors associated with improved outcomes. RESULTS: Eleven Italian hospitals reported data on 706 patients undergoing elective colorectal surgery within an ERAS protocol. Patients with low physical status had reduced adherence to preoperative carbohydrate loading, epidural analgesia, PONV prophylaxis, and early urinary catheter removal. No difference was found between groups for adherence to other perioperative elements. Major complications occurred in 37 (5.2 %) patients without significant differences among groups (p = 0.384). Median (IQR) time to readiness for discharge (TRD) was 4 (3-6) days, length of hospital stay (LOS) was 6 (4-7) days, and both were significantly shorter by only 1 day in the groups of younger patients (p < 0.001). At multivariate analysis, laparoscopy increased adherence to ERAS items and reduced TRD, LOS, and morbidity. A high ASA grade was significantly associated with lower adherence, whereas older age significantly prolonged TRD and LOS. CONCLUSION: ERAS pathway can be safely applied in elderly and low physical status patients yielding slight differences in postoperative morbidity and time to recover. Laparoscopy was independently associated with increased adherence to ERAS protocol and improved short-term postoperative outcome.

Space GlucoseControl system for blood glucose control in intensive care patients--a European multicentre observational study.

BACKGROUND: Glycaemia control (GC) remains an important therapeutic goal in critically ill patients. The enhanced Model Predictive Control (eMPC) algorithm, which models the behaviour of blood glucose (BG) and insulin sensitivity in individual ICU patients with variable blood samples, is an effective, clinically proven computer based protocol successfully tested at multiple institutions on medical and surgical patients with different nutritional protocols. eMPC has been integrated into the B.Braun Space GlucoseControl system (SGC), which allows direct data communication between pumps and microprocessor. The present study was undertaken to assess the clinical performance and safety of the SGC for glycaemia control in critically ill patients under routine conditions in different ICU settings and with various nutritional protocols. METHODS: The study endpoints were the percentage of time the BG was within the target range 4.4 - 8.3 mmol.l(-1), the frequency of hypoglycaemic episodes, adherence to the advice of the SGC and BG measurement intervals. BG was monitored, and insulin was given as a continuous infusion according to the advice of the SGC. Nutritional management (enteral, parenteral or both) was carried out at the discretion of each centre. RESULTS: 17 centres from 9 European countries included a total of 508 patients, the median study time was 2.9 (1.9-6.1) days. The median (IQR) time-in-target was 83.0 (68.7-93.1) % of time with the mean proposed measurement interval 2.0 ± 0.5 hours. 99.6% of the SGC advices on insulin infusion rate were accepted by the user. Only 4 episodes (0.01% of all BG measurements) of severe hypoglycaemia <2.2 mmol.l(-1) in 4 patients occurred (0.8%; 95% CI 0.02-1.6%). CONCLUSION: Under routine conditions and under different nutritional protocols the Space GlucoseControl system with integrated eMPC algorithm has exhibited its suitability for glycaemia control in critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01523665.

External validation of the Simplified Acute Physiology Score (SAPS) 3 in a cohort of 28,357 patients from 147 Italian intensive care units.

OBJECTIVE: To evaluate the SAPS 3 score predictive ability of hospital mortality in a large external validation cohort. DESIGN: Prospective observational study. SETTING AND PATIENTS: A total of 28,357 patients from 147 Italian ICUs joining the Project Margherita national database of the Gruppo italiano per la Valutazione degli interventi in Terapia Intensiva (GiViTI). INTERVENTIONS: None. MEASUREMENT: Evaluation of discrimination through ROC analysis and of overall goodness-of-fit through the Cox calibration test. MAIN RESULTS: Although discrimination was good, calibration turned out to be poor. The general and the South-Europe Mediterranean countries equations overestimated hospital mortality overall (SMR values 0.73 with 95% CI 0.72-0.75 for both equations) and homogeneously across risk classes. Overprediction was confirmed among important subgroups, with SMR values ranging between 0.47 and 0.82. CONCLUSIONS: The result strictly supported by our data is that the SAPS 3 score calibrates inadequately in a large sample of Italian ICU patients and thus should not be used for benchmarking, at least in Italian settings.

Variable costs of ICU patients: a multicenter prospective study.

OBJECTIVE: To analyze the costs of treating critically ill patients. DESIGN AND SETTING: Multicenter, observational, prospective, cohort, bottom-up study on variable costs in 51 ICUs. PATIENTS AND PARTICIPANTS: A total of 1,034 patients aged over 14 years who either spent less than 48 h in the ICU or had multiple trauma, major abdominal surgery, ischemic stroke, chronic obstructive pulmonary disease, cardiac failure, isolated head injury, acute lung injury/adult respiratory distress syndrome (ALI/ARDS), nontraumatic intracranial hemorrhage or coronary surgery. INTERVENTIONS: Data recorded for each patient: length of ICU stay, and cost in euros of all diagnostic and therapeutic procedures, drugs and equipment used, and consultations by physicians from other units. To express cost-efficiency we calculated for each diagnostic group the cost per surviving patient (expenditure for all patients/number of surviving patients) and money loss per patient (expenditure for patients who died/total number of patients). MEASUREMENTS AND RESULTS: Median costs for a multiple trauma patient were euro 4076 and for coronary surgery patient euro 380. The variability is largely due to different lengths of ICU stay. Cost per surviving patient was higher for ALI/ARDS, nontraumatic intracranial hemorrhage, multiple trauma, and emergency abdominal surgery. Money loss per patient was higher for ALI/ARDS and lower for multiple trauma. Planned coronary and major abdominal surgery and short-stay patients were treated most cost-efficiently. CONCLUSIONS: Cost of treatment in an ICU varies widely for different types of patients. Strategies are needed to contain the major determinants of high costs and low cost-efficiency.

Volume of activity and occupancy rate in intensive care units. Association with mortality.

OBJECTIVE: Mortality after many procedures is lower in centers where more procedures are done. It is controversial whether this is true for intensive care units, too. We examined the relationship between the volume of activity of intensive care units (ICUs) and mortality by a measure of risk-adjusted volume of activity specific for ICUs. DESIGN: Prospective, multicenter, observational study. SETTING: Eighty-nine ICUs in 12 European countries. PATIENTS: During a 4-month study period, 12,615 patients were enrolled. INTERVENTIONS: Demographic and clinical statistics, severity at admission and a score of nursing complexity and workload were collected. RESULTS: Total volume of activity was defined as the number of patients admitted per bed per year, high-risk volume as the number of high-risk patients admitted per bed per year (selected combining of length of stay and severity of illness). A multi-step risk-adjustment process was planned. ICU volume corresponding both to overall [odds ratio (OR) 0.966] and 3,838 high-risk (OR 0.830) patients was negatively correlated with mortality. Relative mortality decreased by 3.4 and 17.0% for every five extra patients treated per bed per year in overall volume and high-risk volume, respectively. A direct relationship was found between mortality and the ICU occupancy rate (OR 1.324 and 1.351, respectively). CONCLUSIONS: Intensive care patients, whatever their level of risk, are best treated where more high-risk patients are treated. Moreover, the higher the ICU occupancy rate, the higher is the mortality.