Metabolic support of the critically ill: 2008 update.

Nutrition support in critically ill patients is not merely simple nutrition, but rather metabolic support. In the last few years, the pharmacological properties of nutrients have been specifically addressed in a new field called pharmaconutrition. This review will offer a deeper insight into this field, focusing on the properties of arginine, glutamine, antioxidants, and omega-3 fatty acids as well as the level of blood glycemia which should be maintained in critically ill patients.

Proposal of a flexible structural-organizing model for the Intensive Care Units.

BACKGROUND: The aim of this study was to verify the capability of the Italian Group for the Evaluation of Intervention in Intensive Care Medicine (Gruppo Italiano Valutazione Interventi in Terapia Intensiva, GiViTI) Intensive Care Units (ICUs) in providing high level care (HLC) and to develop a flexible organiziational model, allowing for different levels of care in each ICU. METHODS: Once the number of active beds, personnel and technology of each ICU were determined, we computed whether the available bed number and all available resources could provide HLC according to international standards. For ICUs lacking staff or equipment for safe HLC in all declared beds, we calculated the best combination between HLC and observation/monitoring beds with less need for nurses and technology (low level of care, LLC) in order to optimise the utilization of each bed. We also investigated the work organisation of physicians and nurses in these units. RESULTS: There are 2 070 available beds in the 293 GiViTI ICUs. To provide HLC according to international criteria, the beds would decrease to 80.9%, because 144 ICUs do not have nurses or equipment to provide HLC in each bed. In order to maximize the suitable use of available resources, these ICUs would have to reduce the HLC bed number using the regained nurse workload for LLC. Because of this, the total number of HLC beds would further decrease to 65.9% of all declared beds. During Sundays and holidays, the bed/doctor and the bed/nurse ratios increase in most ICUs. CONCLUSION: To maximize the staff and equipment resources available, the bed numbers of a general ICU providing HLC must vary, even daily, according to the level of care provided. This level is not always high for all patients present. Applying this organizing model to each ICU, we could have enough flexibility to face the different demands for assistance if the ICU is built as a large open space to achieve the best clinical model and use of resources.

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

OBJECTIVES: We 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 SETTING: Multicenter, randomized, unblinded clinical trial in 33 Italian general ICUs. PATIENTS AND PARTICIPANTS: The 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). INTERVENTIONS: Patients were randomized to two arms: early iEN or early PN. MEASUREMENTS AND RESULTS: Primary 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. CONCLUSIONS: Compared 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.

Metabolic treatment of critically ill patients: energy balance and substrate disposal.

Oxidation of substrates is the main biochemical process used by the human body to produce energy. Different substrates (carbohydrates, lipids, and proteins) have different effects on oxygen consumption and carbon dioxide production: during the critical phase of pathologies it could be relevant pay attention to the use of various nutrients, that have some altered effect respect to the normal subjects metabolism, and during the length of metabolic treatment, too. Generally, nutrition lead to replenish body stores, while endogenous substrates are used to be oxidized. Critically ill patients show a preference for prompt energy availability (i.e. glucose) to avoid endogenous protein catabolism; lipids are shown to have a more pronounced storage effect. Adequate amount of energy intake in carbohydrates determine an increase of RQ, that means a shift from a more lipid-based to a more glucose-based oxidation. Composition of dietary intake can be usefully different for each pathology, and also for different periods of the same pathology, because critically ill patients have a variety of metabolic needs during their stay in ICU.

Metabolic treatment of critically ill patients: energy expenditure and energy supply.

Nutrition in critically ill patients should be considered as therapy: assessing the energy expenditure and the termogenic effect of food, and knowing the differences among composition and amount of given substrates, it is possible restore, maintain, or at least limit the derangement of energy equilibrium. Energy metabolism comprehends assumption, storage and oxidation of nutrients: all these factors could be discriminant in critical clinical conditions, particularly cardiac and respiratory failure. Then, this review would lead the decision making process beginning from biochemistry and bioenergetics, until the metabolic strategy practically usable at the bedside of patients during the whole critical phase of their pathology.

Evaluating daily nursing use and needs in the intensive care unit: a method to assess the rate and appropriateness of ICU resource use.

BACKGROUND: We designed a tool to measure the rate and appropriateness of intensive care unit (ICU) nursing coverage as a proxy for the use of resources. METHODS: We tested the tool in 32 Italian ICUs during a cross-sectional study (4 days/week, October 2001 and April 2002). The level of care was classified as high or low. The appropriate patient-to-nurse ratio for both levels (2/1 and 3/1 in this ICU mix) was defined. The provided and theoretical nurse assistance was computed, the difference between the two quantifying the ICU use of personnel: a positive difference means over-utilization, a negative one under-utilization. We calculated the maximum number of high-level and low-level care days available for ICU and the relative utilization rates. These two rates quantify the appropriateness of resource use in relation to the planned use. RESULTS: Analysing 5783 treatment-days, the tool identified units using almost all available resources (five), overcrowded (14: too small units) or empty (16: too big). Units were overcrowded on account of the high-level of care required (five: utilization rate >100%) or reallocated too much of their residual high-care nursing capacity to low-level care (six). In empty units both utilization rates were lower than expected. CONCLUSIONS: The method quantifies the rate and appropriateness of resource usage and suggests the best management in units with fixed human resources or a fixed number of beds.

Effectiveness and efficiency of intensive care medicine: variable costs in different diagnosis groups.

BACKGROUND: To establish the effectiveness of ICU treatment and the efficiency in the use of resources in patients stratified according to 10 diagnosis and two levels-of-care. To propose strategies aimed at reducing costs and improving efficiency in each patient group. METHODS: Multicentre prospective observational study. ICUs enrolled two cohorts of up to 10 consecutive patients with ICU stay >/= 48 h. Each with one of these diagnoses: trauma, brain-trauma, brain-hemorrhage, stroke, acute-on-chronic-obstructive-pulmonary disease, lung-injury/acute respiratory distress syndrome, heart failure, and scheduled/unscheduled abdominal surgery. The presence of active-life support divides high from low level-of-care treatments. Variable ICU costs were collected daily (bottom-up) for 21 days. We evaluated effectiveness (hospital survival) and efficiency (hospital-survivors variable-cost as a ratio of overall cost). RESULTS: Forty-two Italian general ICUs recruited 529 patients in 5 months. Mean ICU variable-costs significantly differed with diagnosis and level-of-care. Costs were positively affected by ICU length-of-stay, by duration of active-treatment. Outcome variably influenced costs. Medians of variable-costs per patient (1715 Euro) and patient-groups efficiencies (60.7%) identified four possible combinations between (low and high) cost and (low and high) efficiency groups. Moreover, efficiency was better than effectiveness in stroke, brain-hemorrhage and trauma, while it was worse in heart failure, acute-on-COPD or acute-lung injury. Overall ICU cost attributed only to survivors ranged from 699 (scheduled surgical) to 5906 (unscheduled surgical) Euro. Cost of non-survivors distributed to all patient was between 95 (scheduled-surgical) to 1633 (unscheduled-surgical) Euro. CONCLUSIONS: Analysis of variable patient-specific cost was used as a tool to assess intensive care performance in patient subgroups with different diagnosis and levels-of-care.

Nutrition given to critically ill patients during high level/complex care (on Italian ICUs).

BACKGROUND & AIMS: Within a prospective study on costs in 45 Italian intensive units we reviewed nutrition support practice given during critical illness. METHODS: From June to October 1999, patients with an ICU stay longer than 47 h were studied. Nutrition (i.e. fasting, parenteral, enteral and mixed) and calorie supply by the enteral route were monitored during the first consecutive days (up to seven) of invasive support of organ failure (high-care). RESULTS: 388 patients received high-care for at least 1 day, 200 patients had seven consecutive high-care-days. Some form of nutrition was given in 90.7% of patients, 9.3% were never fed (25.8% of the cardiac patients). Parenteral nutrition was given in 13.9% of patients (78.9% of the abdominal surgery patients), 39.7% received only enteral nutrition, and 36.4% received mixed nutrition. Finally, 77.1% of the patients received nutrient by gut. Nutrition was given in 78.5% of 2115 collected days, 44.1% of the first high-care-days and 93.5% of the 7th days were positive for nutrition. Enteral calorie load on the first day was similar for enteral and mixed nutrition (range 8-14 kcal/kg), it was higher for exclusive enteral nutrition between the 4th and the 7th day (15-19 vs. 11-14 kcal/kg). It differed according to diagnosis group. CONCLUSIONS: In Italian ICUs, in complex critically ill patients, nutrition is consistently given in critical illness, gut is widely used except in abdominal surgery patients.

Description of trends in the course of illness of critically ill patients. Markers of intensive care organization and performance.

OBJECTIVE: To identify objective trends of the course of illness that might be used as benchmarks in the auditing of the organization/performance of Intensive Care Units (ICU). DESIGN: Retrospective analysis. PATIENTS AND SETTING: A group of 12,615 patients and 55,464 patient-days prospectively collected in 89 ICUs of 12 European countries. METHODS: The complexity of daily care in the ICU was classified as high (HT) or low (LT), according to six activities registered in NEMS,a daily therapeutic index for ICUs. RESULTS: Six trends of clinical course were identified: LT during the whole ICU stay (5,424 patients, mortality 1.8%); HT (3,480 patients, mortality 30.4%); HT followed by LT (2,781 patients, mortality 2.8%); LT followed by HT (197 patients, mortality 39.1%); finally, LT/HT/LT in 298 patients (mortality 10.5%); and HT/LT/HT (mortality 20.1%) in 438 patients. A group of 930 patients had the complexity of treatment increased (mortality 21.1%) and 3,711 patients received both treatments. Low-care before high-care periods had a mean duration of 2.2 +/- 3.5 days, low-care after high-care 2.7 +/- 3.1 days, and between two high-care periods 2.1 +/- 2.2 days. A group of 1,538 'surgical scheduled' patients only received LT, whereas 2,231 received HT (whether or not exclusively). Overall ICU mortality rate was low (3%) and the length of stay short, regardless of diagnosis and complexity of care received. CONCLUSIONS: The use of therapeutic indexes help to classify the daily complexity of ICU care. The classification can be used as an indicator of clinical performance and resource utilization.

Daily classification of the level of care. A method to describe clinical course of illness, use of resources and quality of intensive care assistance.

OBJECTIVE: To develop a simple and comparable clinical method able to distinguish between higher and lower complexities of care in the ICU. DESIGN: Retrospective analysis. SETTING: Database of European ICUs Study I (Euricus-I: including 12,615 patients and 55,464 patient/days), prospectively collected in 89 ICUs of 12 European countries. METHODS AND RESULTS: A panel of experts developed the classification of the complexity of care. Six (in addition to monitoring, two levels of respiratory support--R and r--two levels of circulatory support--C and c--and dialysis) out of the nine items of Nine Equivalents of Nursing Manpower use Score (NEMS), a therapeutic index, were utilised. Two levels of care (LOCs) were defined according to a more (HT) and a less complex (LT) combination of common activities of care. The two LOCs were significantly related to mortality: higher in HT and they rose with increasing cumulative number of HT days. HT accounted for 31,976 NEMS days (57.7%) while 23,488 (42.3 %) were LT. Major respiratory and cardiovascular support accounted for about 80 % of the HT days. Respiratory assistance and monitoring were responsible for an equivalent percentage of LT days. The distribution of the clinical classification of LOCs coincided with that of the managerial scores of LOCs in the literature. CONCLUSIONS: The managerial instrument described uses simple and reliable clinical data. It is able to distinguish between patients with different severity and outcome, and shows that every additional consecutive day spent in ICU as HT increases the probability of death. Moreover, (1) it suggests the possibility of describing the clinical course of illness by relating the complexity/level of medical care to the available technology and staff; (2) using relevant markers of clinical activity, it might be useful to include in quality control programmes.

Measuring complexity/level of care and appropriateness of resource use in intensive care units.

BACKGROUND: Throughout the world, the cost of critical care medicine is increasing more than the overall health care cost. Thus, a higher attention to improve the efficiency of the use of ICU resources is indispensable. The objective of this study was the development of a simple and reliable tool for the evaluation of the appropriateness of ICU utilization. DESIGN: A repeated cross-sectional data collection was performed twice a week, during a 61-day study period. SETTING: Twenty-three Italian general ICUs. PATIENTS: All patients present in the 23 ICUs on the 17 index days. INTERVENTIONS: On each index day, patients were checked for receiving ventilation/CPAP, pulmonary arterial pressure monitoring, intracranial pressure monitoring, vaso-active drug infusion and hemodialysis-ultrafiltration. Simultaneously, each ICU bed was assessed for its technical and personnel facilities in order to estimate the deliverable level of care. RESULTS: A total of 1250 patients were studied, for a total number of 7533 patient-days. The overall occupancy rate per ICU was 83.8% (-range: 54.4% to 96.1%). The high-level occupancy rate (rate of patients requiring high level of care and actually occupying high-facility beds) was 69.4% (range: 25.0% to 149.0%), while the corresponding low-level occupancy rate was 101.1% (range: 31.3% to 329.4%). CONCLUSIONS: Our model clearly showed up a certain degree of inappropriateness in the use of ICU resources. Most of the ICUs (69.6%) used a very large proportion of their high-facility beds for patients who did not need high-level care. Being very simple, our method could represent a useful tool for continuous evaluation of the appropriateness of resource utilization in the ICU.

Early metabolic treatment after liver transplant: amino acid tolerance.

OBJECTIVE: We investigated the amino acid (AA) tolerance during Total Parenteral Nutrition (TPN) in adult patients undergone liver transplant (LTX). DESIGN: The treatment (Glucose and AA), induced on the 2nd postoperative day, was later maintained with 27 kcal/kg Ideal Body Weight (IBW) as glucose and 0.12 (12 patients: protocol #1), 0.18 (10 patients: protocol #2) and 0.25 g nitrogen (N)/kg IBW (13 patients: protocol #3) till end of the 6th postoperative day. The N intake was sequentially modified in protocol #2 and #3 to increase the supply of the amino acid (AA) that resulted in an infusion plasma level below the expected "normal" range (between 1 and 1.6 times the overnight fasting plasma level of volunteer). PATIENTS: 35 consecutive adult patients without diabetes and organ failures for the entire study period. MEASUREMENTS: Plasma AA profile was measured before LTX and at the last TPN day under continuous infusion. During #1 and #2 protocol, many AA resulted below or at the lower range of the norm while, during 0.25 gN/kg IBW infusion, the majority of the administered AA significantly increased with respect to reference values. Nevertheless, they remained in the "normal" plasma range indicating that they were supplied in an optimal amount (particularly the aromatic and sulphurated ones, potentially toxic if liver function is impaired, and the branched chain AA (BCAA) given at consistent dosage: 0.5 g/kg). Arginine resulted significantly increased (Arg: 1.9 times the reference) and cystine (Cys: 0.45), serine (Ser: 0.8) and taurine (Tau: 0.85) remained significantly lower than "normal" as well as the not administered citrulline (Cit: 0.58) and alfa amino butyric acid (Aba: 0.41). The AA (and calorie) load almost balanced the N losses during the 5th (0.411 +/- 0.038) and 6th study day (0.305 +/- 0.019 gN/kg). CONCLUSIONS: 0.25 gN/kg could be considered the minimum N load in the uncomplicated adult LTX recipients, for reassuring a balanced plasma AA pattern and body N turnover in the early postoperative phase.

Kinetic of body nitrogen loss during a whole day infusion and withdrawal of glucose and insulin in injured patients.

OBJECTIVE: To investigate the kinetics of body nitrogen (N) excretion during 24 h glucose infusion (relating glycemia with insulin supply) and during subsequent 24 h saline infusion in injured patients during a full blown stress reaction. To define the lag time between the start of the withdrawal of glucose and insulin infusion, and the modification in the N loss from the body, and the time span to reach the maximum effect and its size. The knowledge of these variables is mandatory to plan short term studies in critically ill patients, while assuring the stability of the metabolic condition during the study period, and also to assess the possible weaning of the effect on protein breakdown during prolonged glucose and insulin infusion. DESIGN: 24-36 h after injury, patients were fasted ( < 100 g glucose) for 24 h (basal day). Thereafter, a 24 h glucose infusion in amount corresponding to measured fasting energy production rate (EPR), clamping glycemia at normal level with insulin supply followed by 24 h saline infusion, was performed. Total N, urea and 3-methyl-histidine (3-MH) in urine were measures on 4 h samples starting from 20th h of the basal day. SETTING: Multipurpose ICU in University Hospital. PATIENTS: 6 consecutive patients who underwent accidental and/or surgical injury, immediately admitted for respiratory assistance (FIO2 < 0.04). Excluded patients were those with abnormal nutritional status, cardiovascular compromise and organ failures. MAIN RESULTS: Patients showed a 33% increase in measured versus predicted fasting EPR and a consistent increase in N and 3-MH urinary loss. An infusion of glucose at 5.95 +/- 0.53 mg/kg x min (97.20 +/- 0.03% of the fasting measured EPR) with 1.22 +/- 0.18 mU/kg x min insulin infusion reduced N and 3-MH loss after a time lag of 12 h. The peak decrease in body N (-36%) and 3-MH loss (-38%) was reached during the first 12 h of glucose withdrawal period. Thereafter, during the following 12 h, the effect completely vanished confirming that it is therapy-dependent and that the metabolic environment of the patients did not change during the three days study period. CONCLUSION: 24 h glucose withdrawal reduces N and 3-MH loss injured patients, the drug-like effect is maintained during the first 12 h of withdrawal and thereafter disappears. The study suggests that at least a 24 h study period is necessary when planning studies exploring energy-protein metabolism relationship in injured patients, and, again 24 h before changing protocol in a crossover study.

Effect of infusion and withdrawl of glucose and insulin on gas exchange in injured ventilated patients.

PURPOSE: To evaluate the effect induced on gas exchange and on urea excretion by glucose and insulin infusion in injured patients. The magnitude and time necessary for the full development of the metabolic effect were investigated. METHODS: Six injured patients were investigated. During the first 24 hours, the fasting period, patients received 1 mg/kg*min of glucose; during the second 24 hours, the treatment period, infusion was increased to about the 95% of the energy production rate; during the last 8 hours, (stop period) the infusion rate was again set to 1 mg/kg*min. Gas exchange was determined in two consecutive 12-hour series, for 30 minutes every hour, either during a stabilized treatment or after its variation. Urea excretion was determinated on 4-hour samples. RESULTS: With respect to the fasting period, during the last 4 hours of the treatment period, the energy production rate did not vary; urea excretion (-25%) and oxygen consumption (-9%) decreased significantly. Carbon dioxide production (+16%), total respiratory quotient, and minute ventilation (+5%) increased significantly. Carbon dioxide production varied linearly with time (glucose infusion +1.74 mL/min*m2*h, P < .05; glucose withdrawal -1.89 mL/min*m2*h, P < .01). Minute ventilation decreased only during the withdrawal period by 65 mL/min*m2*h (P < .05). CONCLUSIONS: The infusion of glucose and insulin, in an amount slightly lower than the metabolic expenditure, leads to a consistently reduced amino acid catabolism and to a decreased oxygen consumption, without affecting energy requirements. Although it leads to an increase of carbon dioxide production, the measured change is so small and slow that it is not harmful unless there is severe respiratory insufficiency.

[Energy metabolism and metabolite flow from muscle tissue during TPN of trauma patients]. / Metabolismo energetico e flusso di metaboliti dal tessuto muscolare durante TPN di pazienti traumatizzati.

AIM: We evaluated muscle-visceral interorgan flux of substrates in 8 critically ill patients in the flow phase after injury. SETTING: This study was conducted on critically ill patients admitted in ICU. PATIENTS: 8 patients were studied immediately after injury. RESULTS: We measured leg flux for oxygen, amino acids, glucose, lactate pyruvate, keton bodies, free fatty acids (FFA), free and total carnitine, and whole body oxygen consumption, nitrogen (N) balance and 3-methyl hystidine (3MEH) excretion during fasting and the second day of metabolic treatment (10.7 +/- 0.06 g x N x m-2 e 1035.5 +/- 3.9 kcal x m-2 x die). During fast the leg shows a net release of N, pyruvate, FFA and free carnitine while glucose, lactate and keton bodies fluxes are not different from zero. The energy balance of the leg is markedly negative (substrate for 79 kcal x m-2 burned for leg energy requirement and 347 kcal x m-2 released as a such). Assuming the body muscle tissue 4.5 times the leg tissue and knowing whole body energy balance, we were able to assess that the non muscular (visceral) part of the body resulted in a consistently positive energy balance. The metabolic treatment is able to match the energy expenditure and the substrate efflux of the leg (and the whole body muscle tissue). In fact the efflux of amino acids and FFA is reduced pyruvate blunted while glucose is remarkably taken up (the uptake of the whole muscle tissue accounted for 72% of the daily load). At the same time, the treatment blunts leg free carnitine and reduces body 3MEH output. Moreover, the caloric balance of the non muscular part of the body remains positive even if the qualiquantitative uptake of substrates is different from fasting. CONCLUSION: Substrates for energy requirements of visceral tissue came from muscular tissue. The metabolic treatment is able to modulate this process.

["ARCHIDIA": a system for patients' data collection and computerized filing. Part I. Methodology]. / Sistema di raccolta dati paziente e archiviazione computerizzata "ARCHIDIA". Parte I--Metodologia.

This report describes a computer based program of patient clinical data collection: the ARCHIDIA system. The project relies on descriptive analysis of clinical events according to well defined methodological criteria. This allows the formulation of a concise diagnosis which is, at the same time, exhaustive of all essential information. Two are the basis principles of this methodology: To define, as accurately as possible, the logical steps necessary to elaborate the diagnosis, that is construed by a sequence of codes. To define all the conditions that must be followed so to use any code in a controlled and independent way. These criteria were derived from literature. The major claim of the system is likely to be the introduction of a "common language" between different ICUs. Uniformed diagnostic and clinical criteria are the main source of large data collection for descriptive, analytic and prospective studies. After a one year pilot study performed by 4 ICUs, ARCHIDIA was used, in 1991, by 20 centers from the area of Milan, Pavia, Como, Varese (70% of total) and 4148 patient data were collected. A descriptive analysis will be reported in the following paper.

["ARCHIDIA": a system for patients' data collection and computerized filing. Part II. General description of a caseload]. / Sistema di raccolta dati paziente e archiviazione computerizzata "ARCHIDIA". Parte II--Descrizione generale della casistica.

OBJECTIVE: To describe a population of patients admitted in ICU in an homogeneous urban area by means of a computed system. EXPERIMENTAL DESIGN: Observational study. SETTING: 20 general intensive care units of general and university hospitals. PATIENTS: Patients admitted in ICU from 1-1-1991 to 31-12-1991. 3 centers collected patients only for 6 months, starting on 1-6-1991. MEASUREMENTS: For each patient demographic data, hospitalization data, outcome, diagnosis and diagnostic procedures used during hospitalization according to defined criteria previously described, were collected. Data have been collected on PC using dedicated software. RESULTS: All centers concluded data collection, none abandoned the study. General characteristics of 4148 valuable patients were reported. Age was 52.9 years, SAPS 12.4 and mortality 21.7%. The patients spent 8.7 days in ICU and, when transferred to a general ward, the following hospitalization was 21.5 days. CONCLUSIONS: Data collection demonstrated the project feasibility. It realizes a continue up to date system inside each unit and allows the use of a "common language" and homogeneous methodology between centers.