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.

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.

Comparative analysis of torasemide and furosemide in liver cirrhosis.

This review concerns studies of the comparative efficacy and safety of torasemide and furosemide in patients with cirrhosis of the liver complicated by ascites and oedema. The short-term trials reviewed indicated that in patients who had failed to respond with adequate diuresis and loss of body weight and ascites to bed rest, restricted salt and water intake and spironolactone, torasemide had a longer duration of action than furosemide and resulted in a greater urinary excretion of salt and water and greater loss of body weight. Torasemide also had less effect than furosemide on urinary potassium excretion and unlike furosemide did not increase the fractional excretion of magnesium or phosphate or the blood ammonia concentration. Two longer term trials in similar patients with decompensated hepatic cirrhosis confirm the results of the shorter term studies. These studies, albeit each in relatively small numbers of patients, confirm the ability of torasemide to enhance diuresis, free water clearance and fractional excretion of sodium and chloride, resulting in loss of body weight and mobilization of ascites in patients with decompensated hepatic cirrhosis. In these patients, the relatively small increase in urinary excretion of potassium, induced by torasemide without any marked effect on renal function or on the plasma neurohormonal profile, enhances its potential safety.

[Retrospective study of Mycobacterium avium complex infection in the acquired immunodeficiency syndrome]. / Studio retrospettivo dell'infezione da Mycobacterium avium complex nella sindrome da immunodeficienza acquisita.

We discuss here our experience with Mycobacterium avium complex (MAC) infection in 446 HIV-positive patients. MAC was found in 13 cases (2.9%): 10 males, 3 females, age range 21-47 years. Infection was disseminated in 10 cases and limited to the lung in 3. CD4+ cells were, on average, 48 per microliters. At clinical onset, all patients suffered from fever and weight loss, 10 from anemia, and 5 from diarrhea. MAC was found in its disseminated form in cultures of blood (10 patients), stool (5 patients) and urine (1 patient). Broncho-alveolar lavage seemed to be the most specific diagnostic method for lung infection. Twelve patients were treated with a multi-drug regimen consisting of an association of 4 or 5 antibiotics, selected on the basis of antibiogram, from the following: clofazimine, rifabutin, ciprofloxacin, ethambutol, isoniazid, amikacin and piazofolin. Mean survival of patients was 91.7%, 83.4%, 71.8% and 58.4% at 4, 5, 6 and 7 months of treatment respectively. Although the mean survival of the treated group is similar to that of untreated patients, multi-drug therapy seems to improve quality of life inasmuch as it brings temperature to normal and enables weight gain. Dissemination was never observed after treatment in patients with pulmonary infection only.

Torasemide versus furosemide in cirrhosis: a long-term, double-blind, randomized clinical study.

The effects of long-term therapy (70 days) with torasemide (20 mg/day), a new loop diuretic, were compared with those of furosemide (50 mg/day) in a randomized double-blind trial. Both drugs were administered in association with spironolactone (200 mg/day) in 28 nonazotemic cirrhotic patients with controlled ascites. The treatments did not modify creatinine clearance and exhibited a similar effect on body weight, urinary volume, and fractional excretion of uric acid, sodium, and chloride. The effect of torasemide on fractional potassium excretion was lower than that of furosemide. Torasemide showed higher sparing effect than furosemide on calcium, inorganic phosphate, and magnesium excretion and stronger action on free water clearance. No changes in serum parameters were induced by either treatment. Two episodes of hepatic encephalopathy occurred in the torasemide group. In view of its effects on sodium and water excretion and on other urinary parameters, torasemide can represent an alternative tool for the long-term treatment of ascites.

[Body, muscle, and visceral nitrogen balance in catabolic patients. Modification with metabolic treatment]. / Bilancio azotato corporeo, muscolare e viscerale in pazienti catabolici. Modificazioni col trattamento metabolico.

In sixteen severely catabolic patients, two different nutritional treatments with the same nitrogen input (0.30 gN.kg-1.die-1) but with a different caloric support: 30 kcal.kg-1.die-1 foe group A and 15 kcal.kg-1.die-1 for group B were infused. Body nitrogen balance (BN), muscle nitrogen balance (BNm) and, calculated as a difference of the two, visceral nitrogen balance were measured in every patient on basal day and on the second day of total parenteral nutrition. Both nutritional treatment reduced the catabolic state in the same amount: this was confirmed by a less negative body BN and by the reduced excretion of 3-MEH and amino acidic catabolic markers. Otherwise in the other compartments the treatments showed different effects: the metabolic support was more reduced by treatment A than it was by B, supplying to visceral compartment a lower nitrogen amount: the nitrogen dismission from muscle compartment, available for visceral tissues, is greater with treatment B than with treatment A. In conclusion, even if both treatments show the same effect on body nitrogen balance, they penalize either one of the examined compartment or the other. To avoid this problem, the study and the use of tissue-specific nutrients are desiderable. Tissue-specific solutions may warrant the balance among body compartment without any further increase of the nitrogen rate.

Plasma amino acid concentration changes during total parental nutrition in critically ill patients.

In 16 critically ill patients with full-blown stress reaction and without severe organ failure, we studied the kinetics of the arterial plasma amino acid (aa) profile during the first 48 h of total parenteral nutrition (TPN) in order to assess the time necessary to reach the steady-state condition during infusion. Each patient was treated with one of three different amino acid solutions giving, with the same nitrogen load, different intakes of individual amino acids. We found four different responses to the administered amino acids. Some amino acids showed a different trend depending on the dose given. At lower doses a steady state was achieved sooner. Plasma levels of amino acids not supplied in the TPN were unaffected or decreased, achieving a steady state at various times during the study period. We conclude that, in critically ill patients, stable arterial plasma amino acid concentrations are obtained within 24 h of starting TPN. In such patients, valid studies of the effect of amino acid solutions may therefore be carried out over short periods of time, thereby minimizing errors due to a fluctuating and unstable clinical state.

[Optimal dose of amino acids administered in total parenteral nutrition (TPN) of malnourished patients]. / Dose ottimale di aminoacidi somministrati durante nutrizione parenterale totale (NPT) di pazienti malnutriti.

A plasmatic concentration for each aminoacid, between 1 and 1.5 times the normal value in fasting healthy subjects, is considered as an optimal target during total parenteral nutrition (TPN) in malnourished patients. We have analyzed the correlation between the aminoacid input and the aminoacid plasmatic concentration during TPN at different aminoacid composition. By exponential regression curves we then calculated the input required to keep each aminoacid plasma concentration in the optimal range.

[Determination of the best amino acid input after orthotopic liver transplantation]. / Determinazione dell'apporto aminoacidico ottimale dopo trapianto ortotopico di fegato.

Ten-three patients were investigated during the early postoperative phase after orthotopic liver transplantation to assess the adequacy of the amino acid (AA) supply during both parenteral (days 1-5) and enteral (days 6-9) nutrition. Plasma AA profile was determined preoperatively, on day 4 and 5 during TPN and on day 8 and 9 during EN, urea production rate was measured every day. Calories input was 28 kcal.kg-.day as glucose, nitrogen intake was 0.25 g.kg- day, supplying individual AA on the basis of previous studies. Urea nitrogen production during TPN (9-11 gN/m2.day) outlines the ability of the transplanted liver to manage the overall nitrogen load. Individual AA plasma profile was considered the expression of an adequate input when comprised between 1 and 1.5 times the normal value, in this respect we obtained adequate levels of all essential AAs. Particularly phenylalanine, methionine and branched chain AA, critical during liver failure, were kept in this range by supplying 68, 48 and 500 mg.kg-1.day. According to AA profile the supply of cystine and tyrosine (conditionally essential AAs), and of histidine, taurine, proline and serine could be safely increased. Not given dispensable AAs (glutamine, asparagine, citrulline and alfa amino butyric) showed a plasma level below the norm and should be added to the diet.

[Changes in the plasma amino acid profile in critically ill patients during total parenteral therapy]. / Variazioni del profilo aminoacidico plasmatico in pazienti critici durante terapia parenterale totale.

The aim of this study was to evaluate the kinetics of arterial plasma amino acid profile during the first 48 h of clinical TPN in order to assess the time necessary to reach the steady-state condition during infusion. Each patient was treated with one of three different amino acid solutions yielding, in the same nitrogen intake, different intakes of individual amino acids. We found four different kinetics for the administered amino acids: an increase of plasma levels immediately after the start of the TPN with no variations during the steady period; the same trend with the steady-state obtained after 6-24 h of TPN infusion; no influence at all; a decrease of fasting plasma levels with the steady-state attained variably during the study period. Each given amino acid showed a different trend partly depending on the supply, suggesting that the steady-state was reached sooner for most amino acids, when the supply was larger. With lower intakes, plasma levels were unaffected or decreased. We conclude that in critically ill patients at least 24 h are needed to obtain stable arterial plasma amino acid concentration during TPN with adequate intakes of amino acid. Knowledge offers the possibility for a quick and accurate assessment of the adequacy of a given preparation (tailored for critically ill patients), it reduces the time span of the study and, as a consequence, the influence of varied metabolic conditions.

Autopresentation of hepatitis B virus envelope antigens by T cells.

Processing and presentation by T cells appear to be limited to antigens that can directly interact with the T-cell surface, thereby overcoming the T-cell inefficiency in antigen capture and internalization. Our study provides evidence that the hepatitis B virus (HBV) envelope proteins can also be efficiently processed and presented by CD4+ and CD8+ T cells to other T cells in a human leukocyte antigen class II-restricted fashion. This phenomenon suggests a receptor-mediated interaction between T cells and the HBV envelope and defines a system that can, we hope, be exploited for the identification of the receptor binding site within the HBV envelope and for the characterization of the putative cellular HBV receptor.

[Surgical risks for cirrhotic patients]. / Il rischio chirurgico nel paziente cirrotico.

Evaluation of the surgical risk in cirrhotic patients undergoing emergency operations must take into account potential anesthesia-related problems, the specific type of operation, and altered liver function. Therefore, (a) the generic surgical risk, (b) the specific surgical risk and (c) the anesthetic risk, must be distinguished. The factors which affect the generic risk are the conditions which can worsen pre-existing liver failure (e.g. cardiopulmonary disease, area of surgical intervention, stage of liver cirrhosis). Splanchnic reflexes as well as lower venous return to the heart are the potential factors which may lead to reduced hepatic blood perfusion and, therefore, represent the specific surgical risk. The anesthetic risk is due to negative interference with the splanchnic circulation by both artificial ventilation and direct pharmacologic vasoconstrictor effects. Finally, the possibility that the patient is positive for HBV or HIV markers must be considered in order to carry out the necessary measures to avoid direct contact with the blood.

Clinical features of hepatitis delta virus infection in a northern Italian area.

Expression of hepatitis delta virus (HDV) markers was investigated in sera from 310 patients with acute hepatitis, 63 chronic hepatitis B surface antigen (HBsAg) carriers and 76 drug addicts positive for at least one serological hepatitis B virus (HBV) marker. Acute HDV infection occurred in 17.1% of the patients with acute hepatitis. Among 40 cases of coinfection, hepatitis was severe in ten and fulminant in three. Only two of the 13 superinfected patients showed a severe hepatitis, but a high percentage (78%) of them developed chronic hepatitis one year after HDV infection. Also in our area parenteral drug addiction represents the main factor of risk for HDV infection. The high prevalence of HDV infection in our area points to the necessity for serological screening for HDV markers in patients with acute and chronic hepatitis.