Gaetano Iapichino

Albumin Replacement in Patients with Severe Sepsis or Septic Shock

BACKGROUND Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. METHODS In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. RESULTS During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. CONCLUSIONS In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).

SAPS 3—From evaluation of the patient to evaluation of the intensive care unit. Part 1: Objectives, methods and cohort description

ObjectiveRisk adjustment systems now in use were developed more than a decade ago and lack prognostic performance. Objective of the SAPS 3 study was to collect data about risk factors and outcomes in a heterogeneous cohort of intensive care unit (ICU) patients, in order to develop a new, improved model for risk adjustment.DesignProspective multicentre, multinational cohort study.Patients and settingA total of 19,577 patients consecutively admitted to 307 ICUs from 14 October to 15 December 2002.Measurements and resultsData were collected at ICU admission, on days 1, 2 and 3, and the last day of the ICU stay. Data included sociodemographics, chronic conditions, diagnostic information, physiological derangement at ICU admission, number and severity of organ dysfunctions, length of ICU and hospital stay, and vital status at ICU and hospital discharge. Data reliability was tested with use of kappa statistics and intraclass-correlation coefficients, which were >0.85 for the majority of variables. Completeness of the data was also satisfactory, with 1 [0–3] SAPS II parameter missing per patient. Prognostic performance of the SAPS II was poor, with significant differences between observed and expected mortality rates for the overall cohort and four (of seven) defined regions, and poor calibration for most tested subgroups.ConclusionsThe SAPS 3 study was able to provide a high-quality multinational database, reflecting heterogeneity of current ICU case-mix and typology. The poor performance of SAPS II in this cohort underscores the need for development of a new risk adjustment system for critically ill patients.

Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial.

CONTEXT Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome (ARDS). OBJECTIVE To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS. DESIGN, SETTING, AND PATIENTS The Prone-Supine II Study, a multicenter, unblinded, randomized controlled trial conducted in 23 centers in Italy and 2 in Spain. Patients were 342 adults with ARDS receiving mechanical ventilation, enrolled from February 2004 through June 2008 and prospectively stratified into subgroups with moderate (n = 192) and severe (n = 150) hypoxemia. INTERVENTIONS Patients were randomized to undergo supine (n = 174) or prone (20 hours per day; n = 168) positioning during ventilation. MAIN OUTCOME MEASURES The primary outcome was 28-day all-cause mortality. Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge, organ dysfunctions, and the complication rate related to prone positioning. RESULTS Prone and supine patients from the entire study population had similar 28-day (31.0% vs 32.8%; relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .72) and 6-month (47.0% vs 52.3%; RR, 0.90; 95% CI, 0.73-1.11; P = .33) mortality rates, despite significantly higher complication rates in the prone group. Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days (25.5% vs 22.5%; RR, 1.04; 95% CI, 0.89-1.22; P = .62) and at 6 months (42.6% vs 43.9%; RR, 0.98; 95% CI, 0.76-1.25; P = .85). The 28-day mortality of patients with severe hypoxemia was 37.8% in the prone and 46.1% in the supine group (RR, 0.87; 95% CI, 0.66-1.14; P = .31), while their 6-month mortality was 52.7% and 63.2%, respectively (RR, 0.78; 95% CI, 0.53-1.14; P = .19). CONCLUSION Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00159939.

Early enteral immunonutrition in patients with severe sepsis: results of an interim analysis of a randomized multicentre clinical trial.

ObjectiveTo compare the mortality of critically ill patients given either enteral feeding with an immune-enhancing formula or parenteral nutrition (PN). We report the results of a planned interim analysis on patients with severe sepsis which was undertaken earlier than planned once a meta-analysis suggested excess mortality in patients with severe sepsis given enteral immunonutrition.DesignRandomised multicentre unblinded controlled clinical trial.SettingThirty-three General Intensive Care Units in Italy.Patients and participantsAmong the 237 recruited patients, 39 had severe sepsis or septic shock; 21 of them received PN.InterventionsEligible patients received either total PN or enteral nutrition, the latter containing extra L-arginine, omega-3 fatty acids, vitamin E, beta carotene, zinc, and selenium.Measurements and resultsThe primary endpoint for the subgroup analysis on patients with severe sepsis was mortality on Intensive Care Unit (ICU). The ICU mortality of patients with severe sepsis given enteral nutrition (EN) was higher than for those given PN (44.4% vs 14.3%; p=0.039). More patients given EN than patients given PN still had severe sepsis when they died (38.9% vs 9.5%, p=0.055). Recruitment of patients with severe sepsis was subsequently stopped.ConclusionsOur results show that enteral immunonutrition, compared to PN, may be associated with excess mortality in patients with severe sepsis.

Nine equivalents of nursing manpower use score (NEMS)

Objectives: To develop a simplified Therapeutic Intervention Scoring System (TISS) based on the TISS-28 items and to validate the new score in an independent database. Design: Retrospective statistical analysis of a database and a prospective multicentre study. Setting: Development in the database of the Foundation for Research on Intensive Care in Europe with external validation in 64 intensive care units (ICUs) of 11 European countries. Measurements and results: Development of NEMS on a random sample of TISS-28 items, cross validation on another random sample of TISS-28, and external validation of NEMS in comparison with TISS-28 scored by two independent raters on the day of the visit to the ICUs participating in an international study. Multivariable regression techniques, Pearsons correlation, and paired sample t-tests were used (significance at p < 0.05 level). Intraclass correlation, rate of agreement, and kappa statistics were used for interrater reliability tests. The TISS-28 items were reduced to NEMS (9 items) in a random sample of 2000 records; the means of the two scores were no different: TISS-28 26.23 ± 10.38, NEMS 26.19 ± 9.12, NS. Cross-validation in a random sample of 996 records; mean TISS-28 26.13 ± 10.38, NEMS 26.17 ± 9.38, NS; R2 = 0.76. External validation on 369 pairs of TISS-28 and NEMS has shown that the means of the two scores were no different: TISS-28 27.56 ± 11.03, NEMS 27.02 ± 8.98, NS; R2 = 0.59. Reliability tests have shown an “almost perfect” interrater correlation. Similar to studies correlating TISS with Simplified Acute Physiology Score (SAPS)-I and/or Acute Physiology and Chronic Health Evaluation II scores, the value of NEMS scored on the first day accounts for 30.4 % of the variation of SAPS-II score. Conclusions: NEMS is a suitable therapeutic index to measure nursing workload at the ICU level. The use of NEMS is indicated for: (a) multicentre ICU studies; (b) management purposes in the general (macro) evaluation and comparison of workload at the ICU level; (c) the prediction of workload and planning of nursing staff allocation at the individual patient level.

Nursing activities score

ObjectivesThe instruments used for measuring nursing workload in the intensive care unit (e.g., Therapeutic Intervention Scoring System-28) are based on therapeutic interventions related to severity of illness. Many nursing activities are not necessarily related to severity of illness, and cost-effectiveness studies require the accurate evaluation of nursing activities. The aim of the study was to determine the nursing activities that best describe workload in the intensive care unit and to attribute weights to these activities so that the score describes average time consumption instead of severity of illness. DesignTo define by consensus a list of nursing activities, to determine the average time consumption of these activities by use of a 1-wk observational cross-sectional study, and to compare these results with those of the Therapeutic Intervention Scoring System-28. SettingA total of 99 intensive care units in 15 countries. PatientsConsecutive admissions to the intensive care units. InterventionDaily recording of nursing activities at a patient level and random multimoment recording of these activities. ResultsA total of five new items and 14 subitems describing nursing activities in the intensive care unit (e.g., monitoring, care of relatives, administrative tasks) were added to the list of therapeutic interventions in Therapeutic Intervention Scoring System-28. Data from 2,041 patients (6,451 nursing days and 127,951 multimoment recordings) were analyzed. The new activities accounted for 60% of the average nursing time; the new scoring system (Nursing Activities Score) explained 81% of the nursing time (vs. 43% in Therapeutic Intervention Scoring System-28). The weights in the Therapeutic Intervention Scoring System-28 are not derived from the use of nursing time. ConclusionsOur study suggests that the Nursing Activities Score measures the consumption of nursing time in the intensive care unit. These results should be validated in independent databases.

Metabolic and nutritional support of critically ill patients: consensus and controversies

The results of recent large-scale clinical trials have led us to review our understanding of the metabolic response to stress and the most appropriate means of managing nutrition in critically ill patients. This review presents an update in this field, identifying and discussing a number of areas for which consensus has been reached and others where controversy remains and presenting areas for future research. We discuss optimal calorie and protein intake, the incidence and management of re-feeding syndrome, the role of gastric residual volume monitoring, the place of supplemental parenteral nutrition when enteral feeding is deemed insufficient, the role of indirect calorimetry, and potential indications for several pharmaconutrients.

The Eldicus prospective, observational study of triage decision making in European intensive care units. Part II: intensive care benefit for the elderly.

Rationale:Life and death triage decisions are made daily by intensive care unit physicians. Admission to an intensive care unit is denied when intensive care unit resources are constrained, especially for the elderly. Objective:To determine the effect of intensive care unit triage decisions on mortality and intensive care unit benefit, specifically for elderly patients. Design:Prospective, observational study of triage decisions from September 2003 until March 2005. Setting:Eleven intensive care units in seven European countries. Patients:All patients >18 yrs with an explicit request for intensive care unit admission. Interventions:Admission or rejection to intensive care unit. Measurements and Main Results:Demographic, clinical, hospital, physiologic variables, and 28-day mortality were obtained on consecutive patients. There were 8,472 triages in 6,796 patients, 5,602 (82%) were accepted to the intensive care unit, 1,194 (18%) rejected; 3,795 (49%) were ≥65 yrs. Refusal rate increased with increasing patient age (18–44: 11%; 45–64: 15%; 65–74: 18%; 75–84: 23%; >84: 36%). Mortality was higher for older patients (18–44: 11%; 45–64: 21%; 65–74: 29%; 75–84: 37%; >84: 48%). Differences between mortalities of accepted vs. rejected patients, however, were greatest for older patients (18–44: 10.2% vs. 12.5%; 45–64: 21.2% vs. 22.3%; 65–74: 27.9% vs. 34.6%; 75–84: 35.5% vs. 40.4%; >84: 41.5% vs. 58.5%). Logistic regression showed a greater mortality reduction for accepted vs. rejected patients corrected for disease severity for elderly patients (age >65 [odds ratio 0.65, 95% confidence interval 0.55–0.78, p < .0001]) than younger patients (age <65 [odds ratio 0.74, 95% confidence interval 0.57–0.97, p = .01]). Conclusions:Despite the fact that elderly patients have more intensive care unit rejections than younger patients and have a higher mortality when admitted, the mortality benefit appears greater for the elderly. Physicians should consider changing their intensive care unit triage practices for the elderly. (Crit Care Med 2012; 40:132–138)

The Eldicus prospective, observational study of triage decision making in European intensive care units: Part I—European Intensive Care Admission Triage Scores*

Objective:Life and death triage decisions are made daily by intensive care unit physicians. Scoring systems have been developed for prognosticating intensive care unit mortality but none for intensive care unit triage. The objective of this study was to develop an intensive care unit triage decision rule based on 28-day mortality rates of admitted and refused patients. Design:Prospective, observational study of triage decisions from September 2003 until March 2005. Setting:Eleven intensive care units in seven European countries. Patients:All patients >18 yrs with a request for intensive care unit admission. Interventions:Admission or rejection to an intensive care unit. Measurements and Main Results:Clinical, laboratory, and physiological variables and data from severity scores were collected. Separate scores for accepted and rejected patients with 28-day mortality end point were built. Values for variables were grouped into categories determined by the locally weighted least squares graphical method applied to the logit of the mortality and by univariate logistic regressions for reducing candidates for the score. Multivariate logistic regression was used to construct the final score. Cutoff values for 99.5% specificity were determined. Of 6796 patients, 5602 were admitted and 1194 rejected. The initial refusal score included age, diagnosis, systolic blood pressure, pulse, respirations, creatinine, bilirubin, PaO2, bicarbonate, albumin, use of vasopressors, Glasgow Coma Scale score, Karnofsky Scale, operative status and chronic disorder, and the initial refusal receiver operating characteristics were area under the curve 0.77 (95% confidence interval 0.76–0.79). The final triage score included age, diagnosis, creatinine, white blood cells, platelets, albumin, use of vasopressors, Glasgow Coma Scale score, Karnofsky Scale, operative status and chronic disorder, and the final score receiver operating characteristics were area under the curve 0.83 (95% confidence interval 0.80–0.86). Patients with initial refusal scores >173.5 or final triage scores = 0 should be rejected. Conclusions:The initial refusal score and final triage score provide objective data for rejecting patients that will die even if admitted to the intensive care unit and survive if refused intensive care unit admission. (Crit Care Med 2012; 40:125–131)

Early enteral immunonutrition vs. parenteral nutrition in critically ill patients without severe sepsis: a randomized clinical trial

ObjectivesWe compared early parenteral nutrition (PN) and early enteral immunonutrition (iEN) in critically ill patients, distinguishing those with and without severe sepsis or septic shock (SS) on admission to intensive care units (ICUs).Design and settingMulticenter, randomized, unblinded clinical trial in 33 Italian general ICUs.Patients and participantsThe study included 326 patients, 287 of whom did not have SS on ICU admission. Eligibility criteria excluded the two tails in the spectrum of critical conditions, i.e., patients either too well or too ill. Of the patients recruited 160 were randomized to iEN (142 without SS) and 166 to PN (145 without SS).InterventionsPatients were randomized to two arms: early iEN or early PN.Measurements and resultsPrimary endpoint was 28-day mortality for all patients and the occurrence of SS during ICU stay for patients admitted without such condition. While 28-day mortality did not differ between iEN and PN (15.6% vs. 15.1%), patients without SS who received iEN had fewer episodes of severe sepsis or septic shock (4.9% vs. 13.1%). ICU length of stay was 4 days shorter in patients given iEN.ConclusionsCompared to parenteral nutrition iEN appears to be beneficial in critical patients without severe sepsis or septic shock. Parenteral nutrition in these patients should be abandoned, at least when enteral nutrition can be administered, even at an initial low caloric content.