Regional anticoagulation and antiaggregation for CVVH in critically ill patients: a prospective, randomized, controlled pilot study.

BACKGROUND: The aim of this study is to assess the efficacy and clinical safety of regional anticoagulation (heparin pre-filter plus post-filter protamine) plus antiaggregation (pre-filter prostacyclin) [Group 1 (G1)] vs. only systemic heparin anticoagulation without antiaggregation [Group 2 (G2)] in critically ill patients with acute renal failure undergoing continuous veno-venous haemofiltration (CVVH). METHODS: One hundred and ten patients were randomized in a prospective, controlled pilot study. G1 patients received 1000 U/h pre-filter heparin, 10 mg/h post-filter protamine sulphate and 4 ng/kg/min pre-filter prostacyclin, while G2 patients received 1000 U/h pre-filter heparin. The haemofilter transmembrane pressure (TMP) and lifespan, as well as the platelet count were observed 1 h before, and at 6, 12, 18, 24 and 36 h from the beginning of CVVH. RESULTS: Haemofilter TMP remained unchanged in G1 while it increased up to three times in G2 (P=0.0002). The median filter lifespan was 68 h in G1 and 19 h in G2. The rate of spontaneous circuit failure was 24% in G1 and 93% in G2 (P=0.0001). The platelet count was stable over the treatment period in G1 while in G2 it decreased progressively (P=0.0073). CONCLUSION: In critically ill patients suffering from acute renal failure, regional anticoagulation with pre-filter heparin and post-filter protamine plus antiaggregation during CVVH is a simple and safe procedure that prevents increases in filter TMP and increases circuit life time compared with systemic anticoagulation with pre-filter heparin only.

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.

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.

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.

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.

Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study--preliminary data.

The preliminary results of an international collaborative study examining premature menopause in fragile X carriers are presented. A total of 760 women from fragile X families was surveyed about their fragile X carrier status and their menstrual and reproductive histories. Among the subjects, 395 carried a premutation, 128 carried a full mutation, and 237 were noncarriers. Sixty-three (16%) of the premutation carriers had experienced menopause prior to the age of 40 compared with none of the full mutation carriers and one (0.4%) of the controls. Based on these preliminary data, there is a significant association between fragile X premutation carrier status and premature menopause.