The increase of endothelial progenitor cells in the peripheral blood: a new parameter for detecting onset and severity of sepsis.

Sepsis is a clinical syndrome characterized by non-specific inflammatory response with evidence of profound changes in the function and structure of endothelium. Recent evidence suggests that vascular maintenance, repair and angiogenesis are in part mediated by recruitment from bone marrow (BM) of endothelial progenitor cells (EPCs). In this study we were interested in whether EPCs are increasingly mobilized during sepsis and if this mobilization is associated with sepsis severity. Our flow cytometry data demonstrate that in the CD34+ cell gate the number of EPCs in the blood of patients with sepsis had a four-fold increase (45 +/- 4.5% p < 0.001) compared to healthy controls (12 +/- 3.6%) and that this increase was already evident at 6 hours from diagnosis (40.6 +/- 4.2 percent), reaching its maximum at 72 hours. Also the percentage of cEPCs identified in the patients with sepsis (35 +/- 4.6% of the CD34+ cell) was statistically different (p < 0.001) compared to that found in the blood of patients with severe sepsis (75 +/- 4.9%). In addition, we proved that at six hours after sepsis diagnosis, VEGF, CXCL8 and CXCL12 serum levels were significantly higher in septic patients compared to healthy volunteers 559 +/- 82.14 pg/ml vs 2.9 +/- 0.6 (p < 0.0001), 189.8 +/- 67.3 pg/ml 15 vs 11.9 +/- 1.6 (p = 0.014) and 780.5 +/- 106.5 pg/ml; vs 190.2 +/- 71.4 (p < 0.001). Our data suggest that the cEPC evaluation in peripheral blood, even at early times of diagnosis, in patients with sepsis can be envisaged as a valuable parameter to confirm diagnosis and suggest further prognosis.

Opioid-free analgesia by continuous psoas compartment block after total hip arthroplasty. A randomized study.

BACKGROUND AND OBJECTIVE: Adequate analgesia is needed after total hip arthroplasty to control pain at rest and during rehabilitation. Our aim was to compare, in a randomized study, the efficacy of two analgesia regimens in control of postoperative pain after total hip arthroplasty: opioid-free continuous psoas compartment block vs. an opioid/non-steroidal anti-inflammatory drugs continuous intravenous infusion. METHODS: In all, 73 patients (ASA I-III), aged 61-82 yr, undergoing total hip arthroplasty were prospectively enrolled in a single-blind randomized trial. Patients were allocated either to the study group (Group A, n = 37) or to the control group (Group B, n = 36). Patients in Group A underwent preoperative placement of a catheter in the psoas compartment and, 30 min before the end of surgery, the catheter was primed with a loading dose of 0.75% ropivacaine (0.4 mL kg(-1)) followed by a continuous infusion of 10 mL h(-1) ropivacaine 0.2% for 48 h. Patients in Group B received, from 1 h before the end of surgery, a continuous intravenous infusion of 0.1% morphine and 0.12% ketorolac at 2 mL h(-1) for 48 h. Both groups received spinal anaesthesia for surgery. Pain scores at rest and after mobilization, amount of rescue analgesia, nausea/vomiting and haemodynamic parameters were recorded. RESULTS: In Group A, median pain scores were very low during the whole study duration both at rest and during physiotherapy in comparison to Group B. Less rescue analgesia was needed and less nausea and vomiting was observed in Group A. CONCLUSIONS: Opioid-free continuous psoas compartment block seems to be an appropriate and reliable technique in providing effective postoperative analgesia at rest and during physiotherapy after total hip arthroplasty when compared to intravenous morphine/ketorolac infusion.

Aspirin effect on early and late changes in acute lung injury in sheep.

OBJECTIVE: There have been several studies that have already explored the potential beneficial role of cyclo-oxygenase (CO) inhibitors on oleic acid (OA)-induced lung injury in different species. These studies report no significant effect of CO inhibition, though thromboxane B2 (TxB2) was effectively blocked. However, recent studies indicate that pre-treatment with aspirin (ASA) preserve gas exchange in OA lung injury in dogs. Aim of our study has been to evaluate the potential beneficial effects of the pre-treatment with low doses of ASA on gas exchange, hemodynamics, respiratory mechanics, prostanoids and lung histology in OA-induced lung injury in sheep. DESIGN: 0.09 ml/kg of OA was administered into the right atrium of 14 anaesthetized sheep. Six received a bolus of ASA (10 mg/kg i.v.) 30 min before OA, the others saline as placebo. MEASUREMENTS AND RESULTS: Pulmonary and tissue gas exchange, pulmonary and systematic hemodynamics, respiratory system mechanics, TxB2 and 6-keto-PGF1 alpha, leukocytes and platelets concentrations were measured throughout the subsequent 3 h and lung histology was effected at end-experiment. The principal findings of our study are: 1) ASA reduces OA-induced early pulmonary vasoconstriction and bronchoconstriction, parallelled by a suppression of TxB2 generation; 2) the late increase in pulmonary artery pressure and airway resistance due to OA is not inhibited by ASA; 3) the early disturbance in pulmonary gas exchange is reduced by ASA, whereas the late severe deterioration is exaggerated by ASA; 4) the stability of tissue exchange ratio (R) at approximately 1 in ASA-group compared to its fall to approximately 0.7 in controls. CONCLUSION: Our findings suggest that ASA: 1) is only effective to treat the very transient TxB2-induced pulmonary vasoconstriction resulting in hydrostatic edema, and it is ineffective, even accentuates, the subsequent major pulmonary endothelial cell injury leading to alveolar flooding that is unrelated to TxB2; 2) has a transient protective effect on the TxB2-induced early bronchospasm; 3) has a biphasic behaviour on gas exchange, with a benefit which lasts only one hour and then results in a worse gas exchange; 4) has an immediate, stabilizing, persisting effect on R, contrasting with its transient effect on pulmonary hemodynamics and PaO2.

The prominent role of thromboxane A2 formation on early pulmonary hypertension induced by oleic acid administration in sheep.

The early increase of pulmonary artery pressure observed in different models of experimentally induced lung injury have been shown to be associated with the release of vasoconstrictive agents by activated platelets. The aim of this study was to evaluate the pattern of these metabolites, in particular TxA2, and the effects of the inhibition of their production by ASA on the modifications of pulmonary hemodynamics induced by oleic acid administration in sheep. Group I (8 sheep) was infused with oleic acid (0.09 ml/kg at 0.02 ml/min) while in group II (6 sheep) ASA (10 mg/kg i.v.) was administered 30 minutes before oleic acid infusion. In group I pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were significantly higher at the end of the infusion while cardiac output (CO) significantly decreased in comparison to baseline values. A marked increase in plasma TxB2 levels paralleled pulmonary hemodynamic changes. Also plasma 6 keto PGF levels increased after OA infusion. The early increase in PAP and PVR was significantly lower in group II (p less than 0.005) while CO did not undergo any significant change. ASA pretreatment significantly blunted the rise of TxB2 concentrations and prevented the elevation of 6 keto PGFa. These results indicate that early pulmonary hypertension in oleic acid induced injury is mainly related to TxA2 released from platelets and leukocytes and that pulmonary hemodynamic changes are significantly inhibited by ASA pretreatment.

An exceptional case of complete neurologic recovery after more than 5-h cardiac arrest.

We describe a case of more than 5 h cardiac arrest in a 60-year-old patient who underwent general anesthesia for a urologic operation. Before extubation, the patient suddenly developed ventricular fibrillation, pulseless ventricular tachycardia and asystole which was immediately treated by advanced life support (ALS) measures. Thirty minutes later seizures developed and were controlled by 200 mg of thiopentone and 10 mg of diazepam. A pattern of ventricular tachycardia, coarse ventricular fibrillation and asystole lasted for nearly 120 min. Termination of resuscitation maneuvers was considered, but long-term life support was continued for 5 h. After this time, peripheral pulses, with a supraventricular tachycardia-like rhythm and regular spontaneous breathing reappeared. Seven hours later, the patient had a Glasgow Coma Scale (GCS) of 5, dilated unresponsive, absence of pupils, and a systolic arterial pressure of 100 mmHg. He was then transferred to intensive care unit (ICU). The morning after, the patient was awake, responded to simple orders, breathing spontaneously, and free from sensomotor deficit. He was, therefore, extubated. Subsequently, other episodes of transitory ST-line upper wave followed by ventricular fibrillation appeared, suggesting Prinzmetal angina. This was successfully treated by percutaneous coronary angioplasty. The first electroencephalogram recorded the day after cardiac arrest showed a mild widespread background slowing. An electroencephalogram 6 days later showed a return to alpha rhythm with only mild theta-wave abnormalities. Four weeks after the first cardiac arrest the patient was discharged. This is an exceptional experience compared with the others reported. We believe that all the efforts must not be given up when such an event occurs during anesthesia and there are optimal conditions for resuscitation maneuvers.

Defibrotide in extracorporeal circulation on healthy rabbits.

Defibrotide, a partially depolymerized DNA fraction obtained from mammalian lung, was found to have significant antithrombotic and fibrinolytic activities. On the basis of this evidence defibrotide could be of clinical value during hemoperfusive treatment. The present study was designed to evaluate the biological tolerance of this technique in a model of extracorporeal circulation, using an original Silastic apparatus, with defibrotide (0.83 mg/kg-1/min-1 after a 50 mg/kg-1 bolus injection) and heparin (0.66 IU/kg-1/min-1 after a 400 IU/kg-1 bolus injection) in ten rabbits (Group 1) and heparin only in ten others (Group 2, control group). In this study defibrotide produced a significantly lower pressure inside the circuit compared to the control group and gave a protective effect against those pathological changes which appeared during extracorporeal circulation and that may be considered omens of a state of shock. However the use of defibrotide in addition to heparin seemed to have a poor effect on platelet and leukocyte count alterations during application of this technique.

Medical simulation in anesthesiology training.

Simulators are more and more widely used in different scientific areas. Through very sophisticated and realistic simulations, they actually permit to teach and demonstrate theoretical or practical notions. Besides, they allow to evaluate a particular performance. In the latest years, the use of simulators has considerably developed in medicine. Anaesthetists have been the first to use and develop simulation. Having the possibility to deal with emergencies and getting accustomed to them without any real risk is an undeniable advantage. Even though the long-term effects due to a simulation session haven't been properly evaluated yet, it is important to bear in mind that simulators are being successfully used in an impressive number of centres in different parts of the world. The activities in the medical simulation centres deal to a certain extent with studying and teaching to manage critical events. This particular discipline, deriving from the aeronautic field, relies upon decision making and teamwork in order to manage the critical event most appropriately. Formative trainings, initially meant for anaesthetists and later on open to other medical categories as well, have been developed. Such courses aimed at establishing the proper interactions between different people with different tasks who are involved in the approach to an emergency rather than the management of the whole scenario. The main drawback of simulation is, however, the high costs required to set a simulation programme, especially as far as the human resources involved are concerned.

Novel drug delivery systems in pain therapy.

Pain is an unpleasant sensory experience resulting from damage to bodily tissues. It is considered a significant public health problem because it affects 1/5 of the world population and causes loss of great amounts of money. Pain reflects a mixture of pathological, psychological and genetic conditions that need deep understanding to be efficiently treated. If under-treated, pain results in serious immune and metabolic problems. Pain management faces many problems that limit its control. For instance, efficiency of pain killers is limited, pain killers give rise to serious side effects and inability of drug administration methods to help in pain control. Technology can overcome some of these problems and the introduction of implantable controlled drug delivery systems (CDDS), manufactured from biodegradable materials, offers a solution. Implantable CDDS provide good level of pain control, as they continuously provide drug, reduce side effects and improve patients' compliance. Biodegradable type of implantable CDDS are polymer based devices that are fabricated to locally deliver drugs in a pre-designed manner. They are currently a focus of research in the field of pain therapy in order to explore their chance to offer an alternative to the conventional methods for drug delivery. This paper aims to highlight the dimensions of pain issue and to overview the basics of drug release from polymers used for CDDS in pain management. In addition, it discusses the recent advances in the technologically designed drug delivery systems in the field of pain medicine and their clinical applications. Future perspectives are also presented.

Role of patient posture during puncture on successful unilateral spinal anaesthesia in outpatient lower abdominal surgery.

BACKGROUND AND OBJECTIVE: Unilateral spinal anaesthesia is a useful anaesthesia technique in lower abdominal surgery, especially in an outpatient setting. Patient posture is pivotal in the achievement of unilateral anaesthesia. Nevertheless, no studies have elucidated the influence of patient posture during the anaesthetic injection on unilaterality. Thus, the aim was to compare the effect of patient posture, during the induction phase of spinal anaesthesia, on block characteristics. METHODS: Eighty patients, ASA I-II, scheduled for unilateral hernioplasty were randomized into two groups. Anaesthesia was performed in lateral position in Group 1 (G1) with operative side down and in sitting position in Group 2 (G2) whose patients were then immediately turned on their lateral side. All patients were maintained for 20 min in lateral position with their operative side down. Hyperbaric bupivacaine 1% 10 mg were used. RESULTS: Unilateral anaesthesia was seen in 80% (32/40) and 12.5% (5/40) of G1 and G2, respectively. The readiness for surgery was faster in G1 (P < 0.0001). The motor block in the non-operative side was stronger in G2 (P < 0.0001). The offset of sensory block was faster in G1 (P = 0.0001). The offset of motor block was slower in G1 (P = 0.0008). The time for voiding was shorter in G1, although not significant. CONCLUSIONS: Lateral posture during the induction of spinal anaesthesia is pivotal for a higher success of unilateral block, a fast readiness to surgery, and a fast recovery. Therefore, this technique can be considered feasible and time-saving for lower abdominal surgery.

Mean platelet volume trend in sepsis: is it a useful parameter?

AIM: Sepsis, as an uncontrolled generalized inflammatory response, involves also the haemostatic mechanisms. Mean platelet volume (MPV) measurement has been available since 1970s, but neither its relationship with platelet count nor the clinical meaning of this relation has been understood in sepsis yet. This study aimed to evaluate both the trend and the relationship between platelet count (PC) and their MPV and to explore their significance in the course of sepsis. METHODS: Seventy septic patients, were recruited in this prospective study. The PC and MPV were measured repeatedly at the enrollment and, thereafter, whenever patient's sequential organ failure assessment (SOFA) score changed by +/-8% up to 5 samples. Standard correlation test, ANOVA for repeated measures, logistic regression and Wilcoxon test were used. RESULTS: The relationship between PC and MPV, expressed as means and frequency distributions, showed a negative correlation (95% CI; r -0.34; P<0.0001) with an inverse trend during sepsis course. The logistic regression showed a three times increase in death probability (95% CI; OR=3.04; P<0.05) of patients with a MPV<9.7 fL at the recruitment time. CONCLUSIONS: The behaviour of platelets and their respective MPV could be an indirect sign of disturbance in platelet production and activity, and bone marrow response in sepsis. Our results could suggest that routine concomitant measurement of PC and MPV trend could be considered as a quick and reliable guide in the assessment of bone marrow response to sepsis evolution.

Prevention of anaphylactic-anaphylactoid reactions to anesthetics in high-risk allergic patients.

To confirm the role of preventive procedures in high-risk allergic patients, immunological tests in vivo for anesthetics were carried out in 251 atopic patients. The 6-month follow-up showed a complete absence of adverse reactions during the clinical use of hypnotic and muscle relaxant drugs. In the case of local anesthetics, five adverse reactions were observed after dental treatment--four were related to a psychogenic mechanism, and one could not be clearly linked to the local anesthetic. It is possible to confirm that the use of a tested drug that yields negative results has a lower probability of inducing anaphylactic-anaphylactoid reactions during anesthesia.

Alterations in the fine structure of the pig liver upon cold ischemia.

The fine structure of the pig liver was examined after 30 min of warm ischemia at 37 degrees C, after 2 h of cold ischemia at 4 degrees C and after 30 min of warm ischemia followed by a further 30 min of cold ischemia. After warm ischemia, limited mitochondrial swelling was observed in hepatocytes. After cold ischemia, alone or following warm ischemia, vesiculation and vacuolation of the hepatocyte cytoplasm and appearance of intrasinusoidal blebs deriving from hepatocytes were observed with different intensity among the animals. These findings suggest that cooling and storing the liver at 4 degrees C may lead to injury, which could negatively influence the viability of the organ, with different intensity from case to case.

[Safety problems in the use of local anesthetics in the dental area]. / Problemi di sicurezza nell'impiego degli anestetici locali in ambito odontostomatologico.

In the last few years particular attention has been given to the adverse reaction to loco-regional anesthesia now widely used in dental practice. It has seemed therefore interesting to investigate the different types of adverse reactions, with particular attention to the anaphylactic-anaphylactoid ones. Although uncommon, these are interesting for the uncertain pathogenesis, the severity of the clinical picture and the complexity of the treatment. In order to find their adequate prevention, a particular approach to risk patients has been suggested to identify the eventual previous anaphylactic-anaphylactoid reactions and the drugs responsible for it. A procedure based on progressive skin test confirmed by a negative incremental challenge test has been worked out. Moreover the need has been felt for a drug surveillance program capable of collecting computerized data which allows real-time investigation of adverse reaction incidence, their typology and finally the effectiveness of prevention. This procedure should further ensure safety in loco-regional anesthesia in dental practice.

[Survey of physical activity and doping in a sample of 6,915 students aged 14-18 years]. / Rilevazione dell'attività motoria e dell'uso di integratori e sostanze dopanti in un campione di 6915 studenti di età compresa fra i 14 e i 18 anni.

AIM: Promoting physical activity is one of the main goals of health-promotion policies. The period of adolescence is characterised by a high rate of abandonment of any physical activity. In this age range, moreover, the risk of assuming substances in order to improve muscular-mass or athletic results is concrete. This study quantifies the involvement in physical activities and substance assumption in a sample of 6915 students aged 14 to 18 years and living in 7 different areas, mostly in northern Italy. METHODS: The survey's tool is an adapted and modified vision of the Youth Risk Behaviour Surveillance questionnaire, created by US Centers for Disease Control and Prevention (CDC). RESULTS: The study showed a high percentage of the sample not involved in any form of physical activity out of school (33.8%), more among girls (44.1%) than boys (21.2%). Between 14 and 18 years, a continuous reduction of involvement in physical activity is evident, while the percentage of totally physically inactive subjects rises from 30.1% to 43%. Finally, 5.6% in our sample admitted to have been using substances to improve muscular-mass or athletic results at least once in the past. CONCLUSION: According to this study, only a minority of the interviewed adolescents is involved in a regular physical activity. In males, using substances to improve physical strength showed to be rather diffused. Specific health promotion projects are suggested.

Experimental study of argon laser-induced microthrombosis during PGI2 infusion.

In order to evaluate the Argon laser-induced microthrombogenesis during prostacyclin (PGI2) infusion on newly formed microcirculation in the rabbit ear chamber, time-space parameters have been calculated in 118 observations subdivided into 4 groups according to the type and size of the vessels irradiated. The observations were carried out without drug treatment, with continuous infusion of pH 10.5 glycine buffer and with continuous infusion of PGI2 at the dosage of 125 ng X kg-1 X min-1 diluted in the glycine buffer. The results indicated that during PGI2 infusion the size of the thrombus, measured by maximal thrombus area, was always significantly less extended than in untreated animals. Moreover, the number of emboli detached during the first 5 min after laser exposure, measured by rate of embolization, during PGI2 infusion in venules and in the larger arterioles was smaller than in untreated animals. The vasoconstriction which usually takes place in the arteriolar vessels--upstream and downstream from the irradiated site--was in no way modified by the infusion of PGI2. Finally, it was noted that glycine buffer infusion showed an unforeseen activity on laser-induced vascular reactivity.

[The use of hydrophobic PALL BB22-15MS filters in cross-infection prevention during anesthesia]. / Impiego dei filtri idrofobici PALL BB22-15MS nella prevenzione delle infezioni crociate in corso di anestesia.

OBJECTIVE: Microbiological testing evaluations of hygienic procedure properties using PALL BB22-15MS filters to prevent contamination of "single use" breathing circuits during anesthesia. DESIGN: Prospective study. SETTING: Two operating rooms in a University hospital. PATIENTS: One hundred and thirty eight patients underwent general anesthesia for urologic surgery procedures. Patients with positive tests for HIV, B and C hepatitis and those considered to be at risk for HIV infection were excluded. The study was divided into five phases on the basis of times of usage of the same circuit for an increasing number of patients: in phase I, microbiological tests were performed on 4 circuits used on 4 different patients; in phase II the same tests were performed on 2 circuits each used on two different groups of three patients; in phase III, a circuit was used on a group of 15 patients and another on a group of 16 patients and the results were analysed; in phase IV a circuit used in a group of 32 patients was evaluated and phase V involved the analysis of a circuit that was used in a group of 65 patients. INTERVENTIONS: A filter was left in place between the patient and the circuit's Y-piece during all phases of anesthesia. The level of microbial contamination of breathing circuits was analysed in order to evaluate the reliability of the procedure. RESULTS: All analysed circuits remained uncontaminated. Staphylococcus hominis was revealed in respiratory circuit no. 6 of phase II, probably as a consequence of secondary contamination. CONCLUSIONS: Our results confirm that this procedure with the routine placement of a PALL BB22-15MS filter at the circuit's Y-piece can provide an adequate level of protection against cross-infections during anesthesia. The hygienic protocol proposed may allow the change of the anesthetic breathing only once a month.

Haemostatic molecular markers in patients undergoing radical retropubic prostatectomy for prostate cancer and submitted to prophylaxis with unfractioned or low molecular weight heparin.

BACKGROUND: Deep vein thrombosis and subsequently pulmonary embolism are the most common causes of increased post-operative morbidity and mortality in patients with pelvic or abdominal cancer. Aim of the study was to evaluate variations in coagulative parameters induced by two accepted primary prophylaxis patterns: standardized low doses of unfractioned heparin (UFH) or single doses of low molecular weight heparin (LMWH) in cancer patients submitted to radical retropubic prostatectomy. METHODS: Fifty patients (45-75 yr) were randomly assigned two groups. Group 1 received UFH (5000 units s.c. x 3 daily); group 2 received calcium nadroparin (single daily dose of 0.3 ml s.c.). In both groups prophylaxis began preoperatively and was maintained throughout the entire hospital-stay. Blood cell, platelet count, coagulative system exploring tests, thrombotic molecular markers, and physiological inhibitors of coagulation were determined at baseline conditions and on the first and seventh day after surgery. RESULTS: Preoperative values of fibrinogen, F1+2 fragment, TAT and D-dimer resulted over normal range in both groups. A significant increase of these markers was observed also during the post-operative period. PT, aPTT, ATIII, PC, total and free PS showed the most substantial changes on the 1st post operative day, though their values ranged within normal levels on the three sampling times. The levels of haemostatic markers demonstrated a baseline hypercoagulability, probably related to cancer and thrombin activation caused by prostatectomy. Despite this thrombophylic state, neither of the two groups presented symptomatic bleeding or thromboembolic complications. CONCLUSIONS: These results prove that a single daily dose of nadroparin has been safe and efficient as a thrice-daily dose of UFH, with a better risk/benefit relationship.