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AIM: The aim of this study is to describe the first experiences on the use of protein C concentrate (PC) in adult patients with severe sepsis and septic shock and clinical contraindications to activated protein C (APC). On the basis of the effectiveness demonstrated by the activated form in sepsis and of the encouraging results expressed in literature of protein C concentrate (PC) mainly about meningococcus fulminating infections, we carried out an observational study on protein C concentrate (PC) with 28-day follow-up and a daily analysis of the hemato-chemical and clinical parameters. Particular attention was paid to the variations in the PC plasma levels, to the modifications of the coagulation system, to the SOFA score as well as to the safety under bleeding risk conditions. METHODS: The study included 7 patients (5 females and 2 males) either with severe sepsis (2). or septic shock (5); one of them had DIC, with PC plasma levels less than 50%. APC could not be administered because of clinical reasons. Patients' mean age was 60.5 years (43-78), the average SAPS II 52.2 (36-72), the pathologies leading to sepsis were lung infections (3). and peritonitis (4). The average time elapsed between the onset of the organ failure and the beginning of treatment with PC was 27.7 hours (12-42). RESULTS: Mortality on day 28 was 42.8% (3 deaths), in all patients the PC plasma levels were brought again to the physiological values. Among the biochemical parameters recorded during the PC infusion, was observed in particular a significant decrease of PDFs, a general rise of the platelet count, and a reduction of the lactic acid levels. No adverse reaction or bleeding complication were seen, even if most of the patients' coagulation was altered or at risk due to neurological problems or repeated surgery. CONCLUSION: In our small number of patients, protein C concentrate has proven to be safe and particularly useful in the control of the coagulopathy triggered and sustained by sepsis.

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AIM: Prophylactic administration of tranexamic acid decreases bleeding and transfusions after cardiac procedures but it is still unclear what the best dose and the most appropriate timing to get the best results are. METHODS: We enrolled 250 patients scheduled for elective, primary coronary revascularization. They were randomly divided into 2 groups. Group H received tranexamic 30 mg x kg(-1) soon after the induction of anaesthesia and a further same dose was added to the prime solution of cardiopulmonary bypass (CPB). Group L received tranexamic acid 15 mg x kg(-1) after systemic heparinization followed by an infusion of 1 mg x kg(-1) h(-1) till the end of the operation. Transfusions of bank blood products, bleeding in the postoperative period and coagulation profile were recorded. RESULTS: We did not find any difference between the groups either with respect to transfusion requirements or with respect to blood loss. CONCLUSION: For elective, first time coronary artery bypass surgery, both dosages of tranexamic acid are equally effective. Theoretically, it seems safer to administer it when patients are protected from thrombus formation by full heparinization.

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BACKGROUND: Optimum transfer of energy from the left ventricle to the arterial circulation requires appropriate matching of these mechanical systems. Left ventricular-arterial coupling describes this relationship between the ventricular elastance (Ees) and arterial elastance (Ea). The ratio of these elastances defines the efficiency of myocardium and provides in our study a useful technique for assessment of the actions of remifentanil. The purpose of this study was to evaluate the effects of remifentanil on ventriculo-arterial coupling in cardiac surgery in patients with coronary artery disease. METHODS: Fourteen patients with coronary artery disease, submitted intraoperatively to cardiac anesthesia for myocardial revascularization, were examined prospectively. With the use of transesophageal echocardiography (TEE) and different dicrotic arterial pressures, we determined the ventricle elastance (Ees), the arterial elastance (Ea) and myocardial efficiency before and after administration of a slow-bolus of remifentanil (1 micro kg(-1)). RESULTS: Remifentanil decreases significantly the ventricular elastance (from 6.09 mmHg ml-1 m(-2) to 4.88) (P < 0.05), with a less, but however, significant decrease of arterial elastance (from 3.68 mmHg ml(-1) m(-2) to 3.13) (P < 0.05). Despite causing simultaneous declines, maintains a good myocardial efficiency (0.64-0.68) with no significant difference. CONCLUSION: Although remifentanil depresses ventricular and arterial elastance, preserves a good left ventricular-arterial coupling and mechanical efficiency, despite a little increase of coupling. However, these effects are maintained only during a slow intravenous infusion and are dose-dependent with impairment of coupling, that may contribute to decline in overall cardiovascular performance, at higher anesthetic dose and rapid infusion in patients with a severe myocardial dysfunction.

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AIM: This study aims to evaluate the management of intensive care beds according to the demands received by the SUEM 118 of Padua. It has been carried out by examining the reports drawn up by SUEM physicians from October 1996 to December 2001. The study rated the number of patients for whom an admission to the Intensive Care Unit (ICU) was required, according to the specific clinical situation at the moment of the request. A secondary objective was to evaluate if the critically ill patients had been admitted and treated in the most appropriate medical facility. METHODS: The research is based on 7 087 reports concerning a population of adult and pediatric patients for whom an ICU bed was required in the period previously mentioned. For each report, it analyses the following data (keeping them anonymous): date of demand, main pathology and severity of clinical condition, sex and age, provenence and destination. RESULTS: Even though the number of annual demands for an ICU bed made to SUEM Central 118 has remained unchanged (approximately 1 350 per year), the number of beds made available in the operating rooms of the Hospital of Padua markedly increased. What has been experienced so far, and the data collected in this study has revealed, was that the requests for an intensive treatment for the overall population (hospitalized and non hospitalized) increased disproportionally in relation to the availability of ICU beds. In fact, the total number of hospitalizations in the different ICUs rose steadily year by year (from 3 495 in 1996 to 4 640 in 2001). CONCLUSION: The Hospital of Padua is a landmark center for patients who need specialized treatment. It is therefore important to increase the assistance and safety standards of its ICUs. In recent years there has been a great need for specialized ICUs either for more aggressive procedures (neurosurgical, cardiosurgical, respiratory, cardiologic, etc.) or for the increased use of adequate and invasive treatment for advanced diseases. The available resources of ICU beds should be more rationally distributed between the peripheral and the Regional Hospitals, since the activation of an ICU bed in the operating theatre is a valid, transient option.

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Long-term maintenance of viability and expression of differentiated hepatocyte function is crucial for bioartificial liver support. We developed a new bioreactor design (ALEX), associated with a new extracellular autologous hepatocyte biomatrix (Porcine Autologous Biomatrix - PBM) support. To test this new bioreactor, we compared it to a standard BAL (BioArtificial Liver) cartridge in a ex vivo model using human plasma added to bilirubin, ammonium and lidocaine. A pathology study was performed on both bioreactors. The results suggest that ALEX allows a maximal contact between the perfusing plasma and the liver cells and a proper hepatocyte support by a cell-to-matrix attachment. ALEX is a suitable cell support bioreactor, guaranteeing long-term maintenance of the metabolic activity of hepatocytes when compared to a standard BAL cartridge.

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OBJECTIVE: The aim of this study is to confirm the effectiveness of auditory brain-stem responses (ABRs) and somatosensory evoked potentials (SEPs) in the diagnosis of brain death (BD). METHODS: ABRs and SEPs were recorded at the same session in 130 BD patients (age range 8-77 years, 81 male and 49 female). Twenty-four cases were submitted to serial recordings from preterminal conditions through BD. RESULTS: ABRs were absent in 92 cases (70.8%), only waves I or I-II were present in 32 cases (24.6%), while in the remaining 6 patients (4.6%) waves V and/or III were still present, excluding the death of the brain-stem. In 4 cases (3.1%) SEPs showed the absence of all components following the cervical N9, preventing the diagnosis of BD. Among 126 cases (96.9%) with preserved cervical N9-N13 SEPs confirmed the absence of brain-stem activity in 122 cases (93.7%), in whom no waves following P11 or P13 were recordable. SEPs excluded the diagnosis of BD in the remaining 4 cases (3.2%) showing preserved P14 and/or N18. In all pre terminal patients the far-field P14-N18 were present, and their disappearance was closely related to the onset of BD. CONCLUSIONS: The combined us of ABRs and SEPs was able to confirm BD in almost all patients, providing an objective confirmation of the diagnosis, and to exclude it in 7 cases, thus improving the reliability of diagnosis.

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BACKGROUND: The number of children requiring sedation for radiological procedures is increasing. Anaesthesiologists are increasingly involved in giving sedation or general anaesthesia in the rooms of the Radiology Department. This activity is not easy, and can be dangerous. The procedure is often performed on an ambulatory basis, so the child must be alert and discharged rapidly after the procedure. METHODS: We reviewed the medical charts of 488 patients in order to evaluate the incidence of complications during deep sedation for diagnostic radiological procedures. The patients were sedated with intravenous thiopental or propofol, or with oral chloral hydrate. All the patients were breathing spontaneously and received only supplemental O(2). RESULTS: We found only a few cases of complications, immediately treated without any recourse to tracheal intubation: respiratory failure with arterial desaturation to 94%, regurgitation, vomiting and persistent cough. CONCLUSIONS: On the basis of our experience, we believe that deep sedation with endovenous drugs guarantees safety and rapid discharge after the procedure.

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BACKGROUND: To validate the accuracy of SAPS II, APACHE III and TRISS for the prediction of mortality in Intensive Care Unit (ICU) at polytrauma patients admission. The outcome of multiple trauma patients is often linked to the degree of physiologic dysfunction and to the extension of anatomic lesions, the age of the patient and the lesion mechanism. METHODS: The study population consisted of 93 cases of multiple injured patients hospitalised at the ICU of the Padua hospital from October 1998 to October 1999; the term polytraumatized patient is referred to patients who have multiple lesions of which at least one potentially endangers, immediately or in a short term, their life. These cases were evaluated with the APACHE III, SAPS II, Revised Trauma Score and Injury Severity Score. The predictive power of each system was evaluated by using decision matrix analysis to compare observed and predicted outcome with a decision criterion of 0.50 and 0.40 for risk of hospital death. RESULTS: All trauma score systems under study showed high accuracy rates, above all if they are used with a 40% positive test. CONCLUSIONS: The prognostic scales used in this study showed a good correlation between expected and observed cases, particularly with TRISS and APACHE III systems. The APACHE III system seems to be the most reliable of the different methods analysed. These prognostic systems are seldom or occasionally used in the ICU, in Padua and in the whole of Italy, so Italian data are not suitable to be compared to international ones. Due to urgency, the importance of the evaluation scales is often underestimated, but even if they require time and attention, they surely can be useful in the evaluation of the treatment, and not only of a polytraumatized patient.

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OBJECTIVE: To assess the relative efficacy of tranexamic acid compared with a control group to decrease bleeding and transfusion requirements in a uniform population undergoing aortic valve replacement. DESIGN: Prospective, randomized, double-blind study. SETTINGS: University hospital. PARTICIPANTS: Adult cardiac surgery patients (n = 300). INTERVENTIONS: Patients were randomized into 2 groups to receive either a total of 5 g of tranexamic acid or a saline solution. Bleeding in the postoperative period, transfusions of bank blood products, coagulation profile, intensive care unit stay, and hospital length of stay were recorded. MEASUREMENTS AND MAIN RESULTS: Postoperative bleeding in patients treated with tranexamic acid was significantly lower compared with the control group (p < 0.0001). Packed red blood cells and fresh frozen plasma usage were reduced in the tranexamic acid group compared with the control group (p = 0.0095 and p < 0.0001). Only 24.5% of tranexamic acid patients received blood products versus 45% of control patients (p < 0.01). There was no significant difference in hematologic and coagulation profiles after the operation between the groups. CONCLUSIONS: Tranexamic acid reduces postoperative blood loss and transfusion requirements in elective aortic valve replacement.

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BACKGROUND: The study was aimed at describing the clinical characteristics of dead patients with acute cerebral lesion and analyzing reasons of the shortage of heart-beating potential organ donors in the Intensive Care Units (ICUs) in the Veneto Region. METHODS: Data have been prospectively recorded in 23 ICUs over six months for deceased patients with acute cerebral lesion (clinical data, death diagnosis) and for any potential organ donor (medical suitability, family interview, organ retrieval). RESULTS: In the ICUs of the Veneto Region in 1998 deceased patients with acute cerebral lesion were 187 per million population (p.m.p.); 317 cases have been studied. Median age was 64 years (range 7-93). Heart-beating death was legally confirmed only in 98/317 cases (31%) against a clinical diagnosis of brain death in 203/317 (64%). Only 82/317 (26%) were considered eligible donors and 48/317 (15%) became real donors (22.8 p.m.p.). Among the remaining 235 cadavers, 105 were over 70 years old. In the group of 130 under 70 years absolute contraindications were present only in 30 and problematical clinical situations were reported in 100. CONCLUSIONS: The number of deaths with acute cerebral lesion represents a sensible index and a key factor for evaluating the potential organ donor pool in small regions and in the single intensive care unit. Collected data demonstrate that in the Veneto Region the efficiency of solid organ retrieval can be improved and that organ donor shortage may depend, beyond family refusal, on clinical and cultural factors that hamper stabilized heart-beating deaths. Most potential donors with age over 70 or problematical clinical situations are preventively excluded by ICUs physicians. To improve organ donation all the patients who die in spite of neuro-intensive treatment should be prevented from circulatory arrest to permit legal declaration of death. Thus more potential organ donors without absolute contraindications could be recovered and time would exist for discussing any problematical situation with experts in organ procurement, particularly in respect to existing urgencies in the waiting list.

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BACKGROUND: The 2% formulation of the intravenous anaesthetic agent, propofol (Diprivan), delivers half the amount of lipid compared with the original 1% formulation. This may provide an acceptable alternative for patients who have an impaired ability to metabolise lipids. METHODS: This study was a multicentre, randomised, open comparison of parallel groups. Seventy-three adult patients undergoing elective craniotomy in neurosurgery were randomised to receive either propofol 1% (10 mg/ml) or propofol 2% (20 mg/ml) for induction and maintenance of anaesthesia. RESULTS: Analysis of induction time (199 s, 1%; 202 s, 2%; p > 0.05) and induction dose (1.13 mg/kg, 1.12 mg/kg; p > 0.05) shows that propofol 1% and propofol 2% are pharmacodynamically equivalent. Both formulations were similar regarding overall administration rates, recovery times, haemodynamic variables and tolerability. Plasma triglyceride levels, were lower in the propofol 2% group compared with the propofol 1% group, and significantly lower (p < 0.05) from 1 to 4 hours after induction. CONCLUSIONS: We conclude that propofol 2% is as effective and as well-tolerated as propofol 1% for anaesthesia and is an acceptable alternative to propofol 1% in patients undergoing elective craniotomy in neurosurgery. The lower lipid load suggests it may be of particular benefit to patients with disorders of lipid metabolism.

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Placebo can be defined as "the idea of recovery." It represents the natural impulse toward recovery that is catalyzed by treatment or even simply by the idea of treatment. Therefore, placebo is not an "active" treatment; it is used in scientific research to discriminate between the actual effect of a drug or therapeutic technique and the result of chance or the will to recover. Even though it is only an idea, placebo can cause improvement and recovery in approximately 30% of the subjects treated with any therapeutic program and for very different pathologies. Acute pathologies are more sensitive to placebo than chronic ones; functional disorders respond better than organic alterations, and so on. The main controversial issues in the methodology of acupuncture research are: placebo, double-blinding, and the intensity of stimulation of needles. The most used placebo method is sham acupuncture, which is the insertion of the needles outside acupuncture points. It is argued that this methodologically incorrect choice leads to studying the importance of the acupuncture point, rather than that of acupuncture as a transdermic stimulation technique.

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The most important factor in the management of alimentary tract bleeding is the adequate localization of the lesion. Small bowel bleeding is a rare entity and determination of the specific anatomic site is difficult. Once stomach, duodenum, or colon origin has been discharged through endoscopy, methods such as angiography and Tc99m RBC scans are appropriate. We present a patient with lower gastrointestinal bleeding secondary to jejunal angiodysplasia associated with jejunal diverticular disease. In the present case, Tc99m RBC scans were used to identify the bleeding site. In cases of lower gastrointestinal bleeding of undetermined origin, we suggest the consideration of both diagnoses (angiodysplasia or diverticular disease) with exploratory celiotomy to resolve these pathologies, particularly in the elderly patient.

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OBJECTIVE: The aim of this work was to study the effect of pre-treatment with parachlorophenylalanine (PCPA) and posttreatment with naloxone on the modulating action on neurogenic inflammation of manual acupuncture and low intensity (5 mAmp), low frequency (5 Hz) electroacupuncture (EA). METHODS: Edema was induced by the subcutaneous administration of 50 micrograms capsaicin in rat paws. Pre-treatment with intraperitoneal PCPA was given for 3 days: 200 mg/Kg on the first day and 100 mg/Kg on the second and third days. Naloxone (1 mg/Kg) was administered at the end of the stimulation. RESULTS: The results show that naloxone and PCPA reduce the anti-edema effect of both manual acupuncture and EA. Combined administration of the two drugs completely eliminated the effect of manual acupuncture, and decreased but did not abolish the effect of electroacupuncture. CONCLUSION: These results indicate that both the opioid and the serotonergic inhibitory control systems are involved in the modulating action of acupunctural stimulation on neurogenic inflammation.

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Stimulation of the auricle is considered to be an effective analgesic technique. The aim of the present study is to establish whether there is a correspondence between somatic inflammation and the appearance of lower resistance points, and moreover, whether the stimulation of such points has an analgesic effect. The study has been conducted on 57 male Sprague-Dawley rats weighing between 120-140 g; 7 of them have been used to determine whether inflammation in the paw leads to the formation of lower resistance points on the auricle. The 50 remaining animals have been divided into 5 groups: Group 1 [12 animals], control were subjected to all manipulations with the exception of the auricle stimulation; Group 2 [12] was stimulated with manual acupuncture in the area corresponding to that observed in the above-mentioned first group of 7 animals; Group 3 [12] was stimulated with 5 Hz and 5 mA; electroacupuncture (EAP) Group 4 [8] and group 5 [6] were treated with acupuncture and with EAP respectively on points believed to be inactive in areas diametrically opposite to the ones observed in the first group. After acupuncture, 100 microg capsaicin in 50 microL of physiological solution were injected subcutis in the dorsal surface of the paw. Edema response was monitored for two hours, with measurement taken every 5 minutes. The results show a reduction in the edema response, only in the group treated with EAP on the appropriate points compared to the control group; no variation was observed in the sham groups. To conclude, the hypothesis of a somatotopic division would seem to be probable, and it would seem that the stimulation of the appropriate areas and the use of an appropriate intensity constitute the two main variables influencing the result.

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OBJECTIVE: To evaluate the effectiveness of single proton emission tomography (SPECT) with 99mTc-HMPAO in the diagnosis of brain death (BD). DESIGN: Prospective study in comatose and brain-dead patients. SETTING: Neurologic ICU. PATIENTS AND METHODS: Fifty comatose patients (age range: 10 days-75 years) were submitted to SPECT study. In 21 of them (42%) reversible factors (e.g., influence of drugs affecting the central nervous system) were present. Thirty-eight patients were clinically brain-dead, while the remaining 12 were tested both in pre-terminal conditions and after the clinical onset of BD. INTERVENTIONS: Brain SPECT following i.v. injection of 99mTc-HMPAO (300-1100 MBq), using a 4-headed gamma-camera (20 min, 360 degrees, 88 images). MEASUREMENTS AND RESULTS: All patients tested in pre-terminal conditions showed preserved brain perfusion. Two of them had flat EEGs despite the absence of any reversible cause of coma; three patients survived, but remained in persistent vegetative states. SPECT confirmed the diagnosis of BD in 45 out of 47 patients (95.7%), clearly showing the arrest of brain perfusion (picture of "empty skull"); in two clinically brain-dead children (aged 10 days and 12 months, respectively) weak perfusion of the basal ganglia, thalamus and/or brain stem was still present, precluding the diagnosis of BD; both of them died a few days later. CONCLUSIONS: Our results confirm the reliability of SPECT in the diagnosis of BD. A problem arises about its effectiveness in brain-dead children, but this seems to be a matter of definition of BD and cerebral viability, rather than a limit of SPECT.

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The modality of needle stimulation in acupuncture is part of the concept of the ìintensityî of the stimulation, a variable indicating the ìdosageî of the treatment administered. In this study we intend to compare the effect of superficial and deep needle insertion in the leg ipsilateral or contralateral to the paw treated with capsaicin. Testing was carried out on 100 male Sprague-Dawley rats weighing 120-140 g, divided into 5 groups according to the treatment received. Group 1 [20 animals] was kept as control; Group 2 [20] received ipsilateral deep acupuncture stimulation; Group 3 [20] received ipsilateral superficial acupuncture stimulation; Group 4 [20] received contralateral deep acupuncture stimulation; Group 5 [20] received superficial contralateral acupuncture stimulation. Results show that both acupuncture modalities are efficient when administered ipsilaterally to the paw where capsaicin is injected, while contralaterally only deep stimulation shows a certain efficiency. It is possible to conclude that deep insertion has a greater efficiency, probably because it affects a greater number of receptors; stimulation is therefore of an intensity greater than that seen in superficial insertion.

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In this study we submitted 24 comatose patients (Glasgow Coma Score <8) to Single Photon Emission Tomography (SPECT) during the clinical course of coma to verify its utility and the relationship between SPECT and CT scan data. SPECT was recorded following i.v. injection of Xe-133 in 17 patients and of Tc-99m-HMPAO or Tc-99m-ECD in the remaining 7. SPECT data recorded during the acute phase of coma did not show a clear correlation between cerebral blood flow (CBF) and outcome. SPECT and CT scan detected abnormalities in the same areas in 6 cases (25%); 6 patients (25%) with focal CT-scan lesions showed no focal CBF alterations in the same regions; conversely, in the remaining 12 cases (50%) SPECT disclosed severe perfusion abnormalities where no lesions were detectable on CT-scan. SPECT allowed us to recognize different regional flow patterns, such as absolute or relative hyperemia or oligoemia, which could not be checked with other means, thus improving patient's management. Apart from cerebral ischemia, there was no relationship between lesions on CT-scan and flow pattern. Our preliminary results suggest that SPECT can improve both the knowledge of patient's neurological conditions and management in comparison to the use of only CT scan.

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