[An index of daily intensive care unit activity]. / Studio sequenziale per giorno indice dell'attività di reparti di Terapia intensiva. GiViTI. Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva.

OBJECTIVE: To set up an index for the evaluation of type of interventions and procedures applied a prerequisite for the evaluation of appropriateness of ICU's activity. DESIGN: Observation prospective study. PATIENTS: 2507 patients out of the 5030 enrolled in the cohort study. MEASUREMENTS: A cross-sectional assessment of the volume and intensity of treatment--level of care--delivered to patients was performed at a preidentified index day. A check list of procedures was utilized. Intensive high level treatment was demonstrated by the application of procedures suggesting one or more organs or vital functions intensively supported. Sub-intensive treatment was defined by the application of procedures indicating monitoring or treatments not exclusively performed in intensive environment. RESULTS: 3955 samples were collected over 9 index days; 2707 (68.3%) resulted in intensive, 1227 (30.7%) subintensive or intermediate and 41 (1%) ward treatments. Out of the intensive samples, 63.4% received only one intensive procedure, while 27.9% two. Ventilatory support was the most frequently (90.4%) utilized intensive procedure. Overall 99% of the samples were characterized by treatments/procedures too invasive for normal ward. CONCLUSIONS: The proposed method gives the opportunity to easily evaluate the level of care and then the appropriateness of ICU care.

Prone positioning improves pulmonary function in obese patients during general anesthesia.

We investigated the effects of prone position on functional residual capacity (FRC), the mechanical properties (compliance and resistance) of the total respiratory system, lung and chest wall, and the gas exchange in 10 anesthetized and paralyzed obese (body mass index more than 30 kg/m2) patients, undergoing elective surgery. We used the esophageal balloon technique together with rapid airway occlusions during constant inspiratory flow to partition the mechanics of the respiratory system into its pulmonary and chest wall components. FRC was measured by the helium dilution technique. Measurements were taken in the supine position and after 15-30 min of prone position maintaining the same respiratory pattern (tidal volume 12 mL/kg ideal body weight, respiratory rate 14 breaths/ min, fraction of inspired oxygen [FIO2]0.4). We found that FRC and lung compliance significantly (P < 0.01) increased from the supine to prone position (0.894 +/- 0.327 L vs 1.980 +/- 0.856 L and 91.4 +/- 55.2 mL/cm H2O vs 109.6 +/- 52.4 mL/cm H2O, respectively). On the contrary, the prone position reduced chest wall compliance (199.5 +/- 58.7 mL/cm H2O vs 160.5 +/- 45.4 mL/cm H2O, P < 0.01), thus total respiratory system compliance did not change. Resistance of the total respiratory system, lung, and chest wall were not modified on turning the patients prone. The increase in FRC and lung compliance was paralleled by a significant (P < 0.01) improvement of PaO2 from supine to prone position (130 +/- 31 vs 181 +/- 28 mm Hg, P < 0.01), while PaCO2 was unchanged. We conclude that, in anesthetized and paralyzed obese subjects, the prone position improves pulmonary function, increasing FRC, lung compliance, and oxygenation.

[Daily survey of procedures as markers of resources utilization]. / Rilevazione giornaliera di procedure come tracciante dell'utilizzo di risorse.

OBJECTIVE: To assess and to follow along the time-span of ICU stay the process of resources allocation and utilization. DESIGN: Prospective study. PATIENTS: A cohort of 778 patients consecutively admitted to 7 multipurpose general ICU in the Milano area were enrolled in a survey of the daily performed interventions/procedures. MEASUREMENTS AND MAIN RESULTS: The majority of diagnostic procedure/interventions were performed during the first two days. The number and quality of interventions were transferred into points obtaining a score system in non-monetary units. The resource allocation process shows a regular trend in the sub-intensive patients who were only monitorized. On the contrary the 258 patients who were intensively treated and survived show a phase of high resource-consumption (about 30 daily points: roughly twice the score of monitorized patients) then followed by a post-intensive phase with a resource consumption resulting in a daily score absolutely equal to the sub-intensive patients. The intensive patients who die show a significantly higher score than survived patients. Both daily and cumulative scores do not show differences among different type of patients. CONCLUSION: The evaluation of the process of resources allocation, even if in non-monetary units enables the knowledge of the trend of ICU costs and allows the elaboration of the appropriate budget mechanism.

[Adequacy of admission in neurosurgical intensive care]. / Appropriatezza dei ricoveri in terapia intensiva neurochirurgica.

OBJECTIVE: The Intensive Care Units of Milano metropolitan area are characterized by difficulties of hospitalization for acutely injured patients due to the low bed availability. We evaluated the problem trying to find out possible solutions. DESIGN: On the day of achieved neurological and neurosurgical stability-defined as the day when the intracranial pressure and jugular venous oxygen saturation monitoring, hyperventilation, osmotic therapy were considered no longer needed--the monitoring procedures and instrumental and/or pharmacological treatments that the patients received were recorded and classified as follows: 1) intensive, 2) intermediate, 3) non-intensive. PATIENTS: All the acutely injured patients admitted at five Neurosurgical ICUs during June-July and October-November 1994 have been studied. Only one of these ICUs had a "sub-intensive unit". MEASUREMENTS AND MAIN RESULTS: 391 patients (29.9%) aneurysms and arteriovenous malformations, 25.1% tumours, 2.8% head injuries, 8.7% spontaneous intracranial haematomas, 13.5% various pathologies) were studied. Out of them 358 had an acute brain failure. 16.5% died during brain failure and 83.5% reached neurological stability within 3 days. When neurological stability was reached 32.1% of patients could be classified as "intensive", 63.6% as "intermediate" and 4.3% as "unintensive". In the four ICUs, without sub-intensive ward facilities, 361 patients were admitted with a total amount of 2292 days of hospitalization. Among them 61.9% were spent for a) patients with no brain injury (32 pts/113 days), b) postoperative patients (113 pts/167 days), c) patients in stable neurological conditions (159 pts/1139 days). Therefore, only 38% of the days recorded were given to patients that needed neurointensive care. CONCLUSION: Out data suggest that the receptivity for acute injured patients could be increased creating recovery room units and intermediate post-intensive units together with a better interchange between general and neurosurgical ICUs.

[Respiratory failure caused by myopathy in severe sepsis]. / Insufficienza ventilatoria da miopatia in corso di sepsi severa.

OBJECTIVE: To describe a generalized myopathic disorder occurred in the convalescence phase of illness of a critically ill patient. SETTING: Neurological Intensive Care Unit. PATIENT: A 43-year-old man with acute leukoencephalopathy and severe sepsis complicated by sustained and prolonged cardiovascular, respiratory and renal failure. After 15 days of complete respiratory autonomy, the patient presented an acute ventilatory failure associated with generalized muscle weakness. Neither a relapse of sepsis nor neurological worsening were detected. MEASUREMENTS AND RESULTS: Electromyogram resulted in normal conduction velocity in both motor and sensitive nervous fibers. Muscular biopsy showed marked fiber size variability with several hypotrophic fibers type II fiber grouping, several areas of degeneration-necrosis with macrophage invasion, dishomogeneous oxidative enzymatic activity, no increase in glycogen or lipid content. CONCLUSIONS: These results excluded critical illness polyneuropathy and all the other known myopathies. Prolonged period of sepsis with multiple organ failure can result in a direct generalized myopathy. This possibility should be kept in mind while treating long term critically ill survivors.

The different inhibiting effect of cholera toxin on two leukemia cell lines does not correlate with their toxin binding capacity.

The murine leukemia cell lines L1210 and WEHI-3B show a very different sensitivity to the cholera toxin (CT). The in vitro growth of L1210 is completely inhibited by 10(-8) M CT, while WEHI-3B growth shows the same inhibition at 10(-11) M. The analysis of membrane ganglioside pattern of the two cell lines shows that in L1210 cells the major component is the GM1a ganglioside while the monosialogangl oside fraction from WEHI-3B is entirely composed of gangliosides of the 'b' series among which GM1b is the more represented. The total cholera toxin binding capacity of the ganglioside extract from L1210 cells is more than hundred fold higher than that of WEHI-3B and this difference is also confirmed by the number of CT receptors/cell and by the binding of FITC-B subunit of CT on the cells. These surprising data are in conflict with the poor sensitivity to CT evidenced by L1210 compared to WEHI-3B cells. In order to clarify this discrepancy we investigated the cAMP accumulation, the cell viability and the clonogenicity of these two leukemia cell lines following the treatment with CT and forskolin (FRSK). The treatment of WEHI-3B cells with CT induces a dramatic increase of intracellular cAMP which highly correlates with cell death and the decrease of clonogenicity and this result is partially obtained by the treatment with FRSK. L1210 cells do not evidence significant cAMP accumulation neither with CT nor with FRSK treatment. These data suggest that the different inhibiting effect of CT on WEHI-3B and L1210 cells does not correlate with their different pattern of gangliosides and the related toxin binding capacity. Further they indicate that the growth inhibition of WEHI-3B cells is closely related with a cAMP-dependent cell killing mechanism, while the inhibition of L1210 growth (produced by high concentration of CT) is mediated by a cAMP independent mechanism.

The prone positioning during general anesthesia minimally affects respiratory mechanics while improving functional residual capacity and increasing oxygen tension.

We investigated the effects of the prone position on the mechanical properties (compliance and resistance) of the total respiratory system, the lung, and the chest wall, and the functional residual capacity (FRC) and gas exchange in 17 normal, anesthetized, and paralyzed patients undergoing elective surgery. We used the esophageal balloon technique together with rapid airway occlusions during constant inspiratory flow to partition the mechanics of the respiratory system into its pulmonary and chest wall components. FRC was measured by the helium dilution technique. Measurements were taken in the supine position and after 20 min in the prone position maintaining the same respiratory pattern (tidal volume 10 mL/kg, respiratory rate 14 breaths/min, FIO2 0.4). We found that the prone position did not significantly affect the respiratory system compliance (80.9 +/- 16.6 vs 75.9 +/- 13.2 mL/cm H2O) or the lung and chest wall compliance. Respiratory resistance slightly increased in the prone position (4.8 +/- 2.5 vs 5.4 +/- 2.7 cm H2O.L-1.s,P < 0.05), mainly due to the chest wall resistance (1.3 +/- 0.6 vs 1.9 +/- 0.8 cm H2O.L-1.s, P < 0.05). Both FRC and PaO2 markedly (P < 0.01) increased from the supine to the prone position (1.9 +/- 0.6 vs 2.9 +/- 0.7 L, P < 0.01, and 160 +/- 37 vs 199 +/- 16 mm Hg, P < 0.01, respectively), whereas PaCO2 was unchanged. In conclusion, the prone position during general anesthesia does not negatively affect respiratory mechanics and improves lung volumes and oxygenation.

Fluctuations in levels of various gangliosides in the different tracts of the oviduct of the frog (Rana esculenta) during the reproductive cycle.

The ganglioside content and pattern have been followed in the different tracts (rectus, convoluted and uterine) of the frog oviduct during the reproductive cycle. The main variations we observed are: a) average higher levels of ganglioside sialic acid in the preovulatory phase, with two peaks in March and April for the convoluted and rectus tract, respectively, and a more homogenous behaviour for the uterine tract; in all three tracts of the oviduct a minimum coincident with the ovulation has been found; b) a balanced presence of sulfolipids and gangliosides in the uterine tract: in fact sulfolipids, whose variations have been determined in a previous work, are higher when gangliosides are lower and vice versa, maintaining nearly constant the total negative charge due to these glycolipids; c) an alternate fluctuation of monosialo- and disialo-gangliosides in the preovulatory phase and a net trend toward the increase of monosialo- and the decrease of disialogangliosides in the postovulatory phase; trisialo-gangliosides are in general less represented and show less marked variations; d) the presence of particular gangliosides in particular moments of the reproductive cycle: Fuc-GM1, a fucosylated ganglioside, is higher than the more represented GM1 during the ovulation, while GD1 alpha, a ganglioside with a sialic acid residue linked to GalNAc, is steadily present in all three tracts after ovulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Intermediate intensive units: definition, legislation and need in Italy.

This paper deals with the definition of intensive care medicine and the organization of different levels of care; intermediate and high level. The organization, facilities and personnel for intermediate care are discussed. The available public data on the organization of intensive medicine and modifications planned by the Legislator are considered. Finally, the usefulness of intermediate care and an estimate of the actual need, based on prospective multicentre ad hoc studies, are discussed.

[Effects of inhalation anesthetics on intracranial pressure and cerebral blood flow velocity]. / Effetti degli anestetici inalatori sulla PIC e sulla velocità di flusso cerebrale.

Inhalation anesthetics diminish cerebrovascular resistance, augmenting cerebral blood flow (CBF) and hematic volume. This may lead to a dangerous increase in intracranial pressure (ICP). It has been observed that isoflurane used in hypocapnia does not appear to cause an increase in ICP equal to that caused by other inhalation anesthetics. The authors aimed to evaluate the effects of isoflurane on ICP and on intracranial vessel reactivity to changes in CO2 using a pulsed intracranial Doppler technique which measures cerebral flow velocity (CFV). A prospective study was performed at the Neurosurgery Clinic of the University of Milan in 10 in-patients due to undergo surgical removal of supratentorial intracranial expansion. Patients were anesthetised with isoflurane 1 MAC in air and O2. The following parameters were monitored: ICP at a spinal subarachnoid level; mean arterial pressure (MAP); cerebral perfusion pressure (CPP); ECG; CFV; EtCO2. The study was subdivided into 5 stages: basal (before induction); hypocapnia lasting 30 min; registration of data for 10 min; stabilisation phase in normocapnia; registration in normocapnia. The results show that during hypocapnia isoflurane causes significant reductions in MAP and CCP whereas ICP and CFV tend to diminish but not significantly. On the contrary, isoflurane in normocapnia causes an increase in ICP and a further and more marked reduction in CPP with a corresponding but not significant increase in CFV. In conclusion, in the light of these results the increase in ICP and the contemporary reduction of MAP would appear to restrict the use of isoflurane in normocapnia in patients with intracranial pathologies.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-related changes in the ceramide composition of the major gangliosides present in rat brain subcellular fractions enriched in plasma membranes of neuronal and myelin origin.

Age-related changes of the ceramide composition of gangliosides were studied in the synaptosomal and myelin fractions from rat brain, carrying plasma membranes of neuronal and glial origin, respectively. The five major gangliosides (GM1, GD1a, GD1b, GT1b, and GQ1b) present in these fractions were separated and quantitated by normal-phase HPLC. Each ganglioside was then fractionated by reverse-phase HPLC into the molecular species carrying a single long-chain base (LCB). The largely preponderant LCBs in the synaptosomal and myelin fractions were the C18:1 and C20:1. The content of C20:1 LCB, generally low at 1 month, increased with age in all analyzed gangliosides and in all subcellular fractions and was greater in the "b series" than in the "a series" gangliosides. Remarkably, GM1 was the only ganglioside where the proportion of LCB 20:1 was higher in the synaptosomal fraction than in the myelin fraction. The fatty acid composition of the C18:1 or C20:1 LCB species of the different gangliosides in the synaptosomal and myelin fractions did not undergo appreciable changes with age. Stearic acid was largely predominant in all the gangliosides of the synaptosomal fraction, more in the C18:1 than in the C20:1 LCB species (80-90% vs. 60-70%). The gangliosides of the myelin fraction were characterized by a lower content of 18:0 and a much higher content of 16:0 and 18:1 fatty acids than those of the synaptosomal fraction. Thus, the ceramide composition is different in the gangliosides of neuronal and myelin origin and appears to be subjected to an age-related control.

Lipid interaction of tetanus neurotoxin. A calorimetric and fluorescence spectroscopy study.

The interaction of Tetanus toxin with phospholipid vesicles containing gangliosides (GD1a, GD1b or GT1b) or phosphatidic acid has been investigated at neutral or acidic pH. Change in the thermotropic properties of the vesicles occurred only after addition of the toxin at acidic pH, and led to surface binding or membrane insertion of the protein, dependent on the physical state of the membrane. Most remarkably, toxin addition at acidic pH to dipalmitoyl-phosphatidylcholine vesicles containing GT1b ganglioside, caused formation of ganglioside microdomains on the vesicle surface.

Fuc-GM1 ganglioside mimics the receptor function of GM1 for cholera toxin.

The ability of Fuc-GM1 ganglioside to mimic the receptor function of GM1 for cholera toxin (CT) has been investigated. For this purpose, rat glioma C6 cultured cells were enriched with Fuc-GM1 and the responsiveness to CT was compared with that of cells enriched with GM1 ganglioside. Fuc-GM1 was taken up by cells as rapidly and to the same extent as GM1. When comparable amounts of ganglioside were associated, the cells enriched with Fuc-GM1 bound the same amount of 125I-CT as did cells enriched with GM1. Under conditions in which GM1- and Fuc-GM1-enriched cells bound comparable amounts of CT, the Fuc-GM1-treated cells accumulated virtually the same amount of cyclic AMP as did GM1-treated cells, and activation of adenylate cyclase was also similar. The lag time preceding the CT-induced cAMP accumulation was the same in Fuc-GM1- and GM1-enriched cells. High-sensitivity isothermal titration calorimetry (ITC) experiments showed that the association constants of CT with Fuc-GM1 or GM1 ganglioside were comparable (4 x 10(7) M-1 and 1.9 x 10(7) M-1, respectively, at 25 degrees C). Also, the association constants of the B-subunit pentamer with Fuc-GM1 or GM1 ganglioside were comparable (about 3 x 10(7) M-1 and 7 x 10(7) M-1, respectively, at 25 degrees C).