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Guido Fanelli,1,2 Giuliano De Carolis,3 Claudio Leonardi,4 Adele Longobardi,5,6 Ennio Sarli,7,8 Massimo Allegri,1,2 Michael E Schatman9 1Anesthesia, Critical Care and Pain Medicine Unit, Division of Surgical Sciences, Department of Medicine and Surgery, University of Parma, 2Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliero Universitaria Parma, Parma, 3Pain Therapy Service, Azienda Ospedaliero Universitaria Pisana, Pisa, 4Department of Drug Addiction Diseases, Local Public Health of Rome, Rome, 5Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, Naples, 6Young Against the Pain (YAP) Group, Parma, 7Progetti Live Surgery, 8PinHub Group, Florence, Italy; 9Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA Background: Despite growing interest in the therapeutic use of cannabis to manage chronic pain, only limited data that address these issues are available. In recent years, a number of nations have introduced specific laws to allow patients to use cannabis preparations to treat a variety of medical conditions. In 2015, the Italian government authorized the use of cannabis to treat several diseases, including chronic pain generally, spasticity in multiple sclerosis, cachexia and anorexia among AIDS and cancer patients, glaucoma, Tourette syndrome, and certain types of epilepsy. We present the first snapshot of the Italian experience with cannabis use for chronic pain over the initial year of its use.Methods: This is a retrospective case series analysis of all chronic pain patients treated with oral or vaporized cannabis in six hubs during the initial year following the approval of the new Italian law (December 2015 to November 2016). We evaluated routes of administration, types of cannabis products utilized, dosing, and effectiveness and safety of the treatment.Results: As only one of the six centers has extensively used cannabinoids for intractable chronic pain (614 patients of 659), only the population from Azienda Ospedaliero Universitaria Pisana (Pisa) was considered. Cannabis tea was the primary mode of delivery, and in almost all cases, it was used in association with all the other pain treatments. Initial and follow-up cannabinoid concentrations were found to vary considerably. At initial follow-up, 76.2% of patients continued the treatment, and

Objective The transversus abdominis plane (TAP) block is a relatively simple regional anesthesia technique which entails the injection of local anesthetics (LA) into the interfascial plane between the internal oblique and transversus abdominis muscles, where nerves supplying the anterolateral abdominal wall course. It is widely used for acute pain management following abdominal surgical procedures. We describe a series of cases in which TAP blocks were used to aid in the diagnosis and treatment of chronic abdominal wall pain (CAWP). Design Consecutive case series of 5 patients presenting with CAWP. Setting Regional referral Center for Pain Medicine of the academic tertiary hospital of Parma, Italy. Results Five patients received TAP blocks with LA and steroid. Four patients reported ≥50% pain relief within hours of the procedure, and 2 of them maintained low pain intensities at 6 and 12 months’ follow-up calls. Conclusions TAP blocks are a valuable addition to the diagnostic armamentarium of pain physicians confronted with abdominal pain of unclear origin. Although most patients responded to the LA injection, the varying degrees of response duration may have been influenced by the different etiologies underlying each condition and the variable expressions of placebo responses. Once the abdominal wall and/or its nerves are identified as pain generators, the optimal therapeutic management remains to be determined. Available literature as well as our case series show that long-term benefit may be obtained with 1 or more injections, but we speculate that this may only be the case for pain with predominantly neuropathic components. This article is protected by copyright. All rights reserved.

Background. Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption after laparoscopic surgery. The aim of this multicenter double-blind randomized controlled trial was to assess the efficacy of different doses and dose-related absorption of ropivacaine when nebulized in the peritoneal cavity during laparoscopic cholecystectomy. Methods. Patients were randomized to receive 50, 100, or 150 mg of ropivacaine 1% by peritoneal nebulization through a nebulizer. Morphine consumption, pain intensity in the abdomen, wound and shoulder, time to unassisted ambulation, discharge time, and adverse effects were collected during the first 48 hours after surgery. The pharmacokinetics of ropivacaine was evaluated using high performance liquid chromatography. Results. Nebulization of 50 mg of ropivacaine had the same effect of 100 or 150 mg in terms of postoperative morphine consumption, shoulder pain, postoperative nausea and vomiting, activity resumption, and hospital discharge timing (>0.05). Plasma concentrations did not reach toxic levels in any patient, and no significant differences were observed between groups (P>0.05). Conclusions. There is no enhancement in analgesic efficacy with higher doses of nebulized ropivacaine during laparoscopic cholecystectomy. When administered with a microvibration-based aerosol humidification system, the pharmacokinetics of ropivacaine is constant and maintains an adequate safety profile for each dosage tested.

Herpes zoster (HZ) is an acute viral illness characterized by a vesicular rash with unilateral distribution, which can also result in severe complications such as post-herpetic neuralgia (PHN), ophthalmic zoster, stroke or other neurological complications. The estimate incidence in Europe ranges between 2.0 and 4.6 cases per 1,000 person-years, with a sharp increase in >50 year-old subjects. Currently, treatment options for HZ are only partially effective in limiting the acute phase, while the management of complications is complex and often unsatisfactory. The total burden of the disease and the high costs related to its diagnostic and therapeutic management led researchers to develop a new preventive approach through a live attenuated virus vaccine. The currently available vaccine, with a high antigen content, is safe, well tolerated and reduces the incidence of HZ, PHN and the burden of illness. Several countries have introduced this vaccination, albeit with different recommendations and methods of financing. Taking into account the barriers to this immunization registered in some areas (difficulty of vaccine distribution, lack of physician recommendations, the cost of vaccine for patients, etc.), this group of Italian experts advocate that a common strategy able to guarantee a good compliance with this vaccination should be implemented. The same group addresses some practical questions concerning the use of zoster vaccine.

Clinical management of breakthrough cancer pain (BTcP) is still not satisfactory despite the availability of effective pharmacological agents. This is in part linked to the lack of clarity regarding certain essential aspects of BTcP, including terminology, definition, epidemiology and assessment. Other barriers to effective management include a widespread prejudice among doctors and patients concerning the use of opioids, and inadequate assessment of pain severity, resulting in the prescription of ineffective drugs or doses. This review presents an overview of the appropriate and inappropriate actions to take in the diagnosis and treatment of BTcP, as determined by a panel of experts in the field. The ultimate aim is to provide a practical contribution to the unresolved issues in the management of BTcP. Five 'things to do' and five 'things not to do' in the diagnosis and treatment of BTcP are proposed, and evidence supporting said recommendations are described. It is the duty of all healthcare workers involved in managing cancer patients to be mindful of the possibility of BTcP occurrence and not to underestimate its severity. It is vital that all the necessary steps are carried out to establish an accurate and timely diagnosis, principally by establishing effective communication with the patient, the main information source. It is crucial that BTcP is treated with an effective pharmacological regimen and drug(s), dose and administration route prescribed are designed to suit the particular type of pain and importantly the individual needs of the patient.

Study objective The study objective is to identify differences in postoperative pain management according to different analgesic treatments, targeting 2 main pathways involved in pain perception. Design The design is a randomized, parallel groups, open-label study. Setting The setting is in an operating room, postoperative recovery area, and surgical ward. Patients There are 200 patients undergoing open inguinal hernia repair (IHR) with tension-free technique (mesh repair). Interventions The intervention is a randomization to receive ketorolac (group K) or tramadol (group T) for 3 days after surgery. Measurements The measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the postoperative (up to 5 days) period, chronic pain incidence (1 and 3 months), side effects, and complications. Main results We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in group K vs 32% in group T, P = .43); the proportion of patients with NRS ≥4 was similar in both groups, and the time trajectories were not significantly different ( P for interaction=.24). Side effects were higher (12% vs 6%) in the tramadol group, although not significantly ( P = .14), with a case of bleeding in the ketorolac group and higher incidence of constipation in tramadol group. One patient in each group developed chronic pain. Conclusions Ketorolac or weak opioids are equally effective on acute pain and on persistent postsurgical pain development after IHR, and drug choice should be based on their potential side effects and patient's comorbidities. Further studies are needed to standardize the most rational approach to prevent persistent postsurgical pain after IHR.

BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative pain management by minimizing side effects related to IV opioids and improving patient outcome. The safety profile of different drugs can be better estimated by comparing their pharmacokinetic profiles than by considering their objective side effects. Because levobupivacaine and ropivacaine have different pharmacokinetic properties, our aim was to investigate whether there is a difference in the pharmacokinetic variability of the 2 drugs in a homogeneous population undergoing continuous epidural infusion. This double-blind, multicenter, randomized, controlled trial study was designed to compare the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine 0.125% or ropivacaine 0.2% for postoperative pain management in adult patients who had undergone major abdominal, urological, or gynecological surgery. This study is focused on the evaluation of the coefficient of variation (CV) to assess the equivalence in the systemic exposure and interindividual variability between levobupivacaine and ropivacaine and, therefore, the possible differences in the predictability of the plasmatic concentrations of the 2 drugs during thoracic epidural infusion. METHODS: One hundred eighty-one adults undergoing major abdominal surgery were enrolled in the study. Patients were randomized to receive an epidural infusion of levobupivacaine 0.125% + sufentanil 0.75 μg/mL or of ropivacaine 0.2% + sufentanil 0.75 μg/mL at 5 mL/h for 48 hours. The primary end point of this study was to analyze the variability of plasma concentration of levobupivacaine and ropivacaine via an area under the curve within a range of 15% of the CV during 48 hours of continuous epidural infusion. The CV shows how the concentration values of local anesthetics are scattered around the median concentration value, thus indicating the extent to which plasma concentration is predictable during infusion. Secondary end points were to assess the pharmacologic profile of the local anesthetics used in the study, including an analysis of mean peak plasma concentrations, and also to assess plasma clearance, side effects, pain intensity (measured with a verbal numeric ranging score, i.e., static Numeric Rating Scale [NRS] and dynamic NRS]), and the need for rescue doses. RESULTS: The comparison between the 2 CVs showed no statistical difference: the difference between area under the curve was within the range of 15%. The CV was 0.54 for levobupivacaine and 0.51 for ropivacaine (P = 0.725). The plasma concentrations of ropivacaine approached the Cmax significantly faster than those of levobupivacaine. Clearance of ropivacaine decreases with increasing patient age. There were no significant differences in NRS, dynamic NRS scores, the number of rescue doses, or in side effects between groups. CONCLUSIONS: Considering the CV, the interindividual variability of plasma concentration for levobupivacaine and ropivacaine is equivalent after thoracic epidural infusion in adults. We found a reduction in clearance of ropivacaine depending on patient age, but this finding could be the result of some limitations of our study. The steady-state concentration was not reached during the 48-hour infusion and the behavior of plasma concentrations of ropivacaine and levobupivacaine during continuous infusions lasting more than 48 hours remains to be investigated, because they could reach toxic levels. Finally, no differences in the clinical efficacy or in the incidence of adverse effects between groups were found for either local anesthetic., Published ahead of print May 14, 2015

Objective: The sex of the patients has been shown to affect postoperative pain and morphine consumption; still a clear understanding able to explain the reasons behind this difference struggles to emerge. Our research aimed to investigate one specific aspect of the variability in morphine consumption between sexes. Previous studies have shown that circadian rhythm can influence opioid consumption. Furthermore, circadian rhythm is different between female and male. Our analysis investigated the presence of differences in daily rhythmicity of morphine consumption between males and females. Design: This is a secondary analysis of data collected during 2 years long multicenter clinical trial (NCT01233752). Settings: Clinical data were collected in two Italian hospitals: IRCCS Foundation Policlinico S. Matteo (Pavia) and San Gerardo Hospital (Monza). Patients: The authors recorded data about morphine consumption in 157 patients who underwent major abdominal surgery, who received morphine intravenous patient-controlled analgesia (IV-PCA) as postoperative analgesia. Interventions: The authors analyzed the daily periodicity of effective boluses delivered by morphine IV-PCA with Poisson multilevel models, adjusted by the time of start for each pump. An effective bolus was defined as a correctly delivered bolus of 1 mg of morphine. The authors also evaluated the interactions among the time of the day and sex, age (

Background The aim of this randomised, clinical trial was to compare safety and efficiency of hyperbaric prilocaine and mepivacaine at a dosage of 0.5 ml each for perianal outpatient surgery in terms of transient neurologic symptoms (TNS) and postoperative recovery.

Background This prospective, observer-blinded, randomised, multicentre study aimed at determining the non-inferiority of 50 mg of plain 1% 2-chloroprocaine vs. 10 mg of 0.5% plain bupivacaine in terms of sensory block onset time at T10 after spinal injection. The study hypothesis was that the difference in onset times of sensory block to T10 between the two drugs is ≤ 4 min. Methods One hundred and thirty patients undergoing lower abdominal or lower limb procedures (≤ 40 min) were randomised to receive one of two treatments: 50 mg of plain 1% 2-chloroprocaine (Group C, n = 66) or 10 mg of plain 0.5% bupivacaine (Group B, n = 64). Times to sensory and motor block onsets, maximum sensory block level, readiness for surgery, regression of sensory and motor blocks, first analgesic requirements, unassisted ambulation, home discharge, and side effects after 24 h and 7 days were registered blindly. Results Chloroprocaine was comparable with plain 0.5% bupivacaine in terms of time to sensory block at T10 level. Group C showed faster onsets of motor block (5 vs. 6 min), maximum sensory block level (8.5 vs. 14 min), resolution of sensory (105 vs. 225 min) and motor (100 vs. 210 min) blocks, unassisted ambulation (142.5 vs. 290.5 min), first analgesic requirement (120 vs. 293.5 min), and home discharge (150 vs. 325 min) (all comparisons, P

Background:Low back pain (LBP) is a very frequent condition, affecting most people at some point throughout their life. This cross-sectional study was aimed to investigate a selected panel of cytokines and inflammatory biomarkers in patients with or without LBP.Methods:The study population consisted of 104 patients diagnosed with LBP (52 non-persistent and 52 persistent) and 52 healthy subjects with no LBP. Blood samples were collected for assessment of adiponectin, leptin, monocyte chemoattractant protein-1 (MCP-1) and C reactive protein (CRP). The duration of LBP was categorized as “no pain”, “non-persistent LBP” and “persistent LBP”.Results:Higher values of CRP and lower concentrations of both leptin and MCP-1 were found in LBP patients compared to controls, whereas adiponectin did not differ among groups. MCP-1 was also lower in patients with non-persistent than in those with persistent LBP. Age, leptin (relative risk, 11.8; 95% CI, 3.9–35.8) and MCP-1 (relative risk, 2.7; 95% CI, 1.7–4.4) were independently associated with presence and duration of LBP. The combination of age, leptin and MCP-1 predicted 61% of the risk of LBP duration. The area under the curve of MCP-1 for distinguishing persistent from non-persistent LBP was 0.65 (95% CI, 0.54–0.76).Conclusions:Then results of our study suggest that leptin and MCP-1 may be promising biomarkers for diagnosis of acute LBP and its risk to become chronic.

Regional anesthesia: the best is yet to come

In recent decades, there has been a revision of the role of institutional review boards with the intention of protecting human subjects from harm and exploitation in research. Informed consent aims to protect the subject by explaining all of the benefits and risks associated with a specific research project. To date, there has not been a review published analyzing issues of informed consent in research in the field of genetic/Omics in subjects with chronic pain, and the current review aims to fill that gap in the ethical aspects of such investigation. Despite the extensive discussion on ethical challenges unique to the field of genetic/Omics, this is the first attempt at addressing ethical challenges regarding Informed Consent Forms for pain research as the primary focus. We see this contribution as an important one, for while ethical issues are too often ignored in pain research in general, the numerous arising ethical issues that are unique to pain genetic/Omics suggest that researchers in the field need to pay even greater attention to the rights of subjects/patients. This article presents the work of the Ethic Committee of the Pain-Omics Group (www.painomics.eu), a consortium of 11 centers that is running the Pain-Omics project funded by the European Community in the 7th Framework Program theme (HEALTH.2013.2.2.1-5—Understanding and controlling pain). The Ethic Committee is composed of 1 member of each group of the consortium as well as key opinion leaders in the field of ethics and pain more generally.

Chronic low back pain (CLBP) is a chronic pain syndrome in the lower back region, lasting for at least 3 months. CLBP represents the second leading cause of disability worldwide being a major welfare and economic problem. The prevalence of CLBP in adults has increased more than 100% in the last decade and continues to increase dramatically in the aging population, affecting both men and women in all ethnic groups, with a significant impact on functional capacity and occupational activities. It can also be influenced by psychological factors, such as stress, depression and/or anxiety. Given this complexity, the diagnostic evaluation of patients with CLBP can be very challenging and requires complex clinical decision-making. Answering the question “what is the pain generator” among the several structures potentially involved in CLBP is a key factor in the management of these patients, since a mis-diagnosis can generate therapeutical mistakes. Traditionally, the notion that the etiology of 80% to 90% of LBP cases is unknown has been mistaken perpetuated across decades. In most cases, low back pain can be attributed to specific pain generator, with its own characteristics and with different therapeutical opportunity. Here we discuss about radicular pain, facet Joint pain, sacro-iliac pain, pain related to lumbar stenosis, discogenic pain. Our article aims to offer to the clinicians a simple guidance to identify pain generators in a safer and faster way, relying a correct diagnosis and further therapeutical approach.

Manuela De Gregori,1-3,* Valeria Scotti,4,* Annalisa De Silvestri,4 Moreno Curti,4 Guido Fanelli,2,5,6 Massimo Allegri,2,5,6 Michael E Schatman,2,7 1Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 2Study In Multidisciplinary PAin Research Group, Parma, Italy; 3Young Against Pain Group, Parma, Italy; 4Center for Scientific Documentation and Biometry Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 5Anesthesia, Critical Care, and Pain Medicine, Department of Surgical Sciences, University of Parma, Italy; 6Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliero, Universitaria di Parma, Parma, Italy; 7US Pain Foundation, Bellevue, WA, USA *These authors contributed equally to this work. Abstract: In this study, we investigated the impact of scientific publications of the Italian SIMPAR (Study In Multidisciplinary PAin Research) group by using altmetrics, defined as nontraditional metrics constituting an alternative to more traditional citation-impact metrics, such as impact factor and H-index. By correlating traditional and alternative metrics, we attempted to verify whether publications by the SIMPAR group collectively had more impact than those performed by its individual members, either in solo publications or in publications coauthored by non-SIMPAR group investigators (which for the purpose of this study we will refer to as “individual publications”). For all the 12 members of the group analyzed (pain therapists, biologists, and pharmacologists), we created Open Researcher and Contributor ID and Impact Story accounts, and synchronized these data. Manually, we calculated the level metrics for each article by dividing the data obtained from the research community by those obtained from the public community. We analyzed 759 articles, 18 of which were published by the SIMPAR group. Altmetrics demonstrated that SIMPAR group publications were more likely to be saved (77.8% vs 45.9%), discussed (61.1% vs 1.1%, P

The physiology of inflammatory response is modified by the aging process and is substantially affected by multimorbidity and disability. Infection is the most frequent cause of acute inflammation in both adult and older subjects. C-reactive protein (CRP) is the most used biomarker of inflammation, and a substantial amount of literature has demonstrated its importance and clinical usefulness in adult subjects. However, the clinical significance of serum CRP determination has not been completely clarified in older subjects with acute infection, especially in the light of the age-related rearrangements in immunity and cytokine production. Thus, in the present review, we focus on the existing knowledge about serum CRP level interpretation in geriatric patients hospitalized with acute infection. Our aims were to determine the significance of CRP measurement at hospital admission for establishing a diagnosis of infection and/or a prognosis and to evaluate whether it is indicated to repeat hs-CRP measurements during hospital stay for monitoring disease course and, possibly, guiding the discharge timing. We concluded that CRP dosage at hospital admission is helpful to detect acute infection, and particularly sepsis, in geriatric patients, and that CRP elevation may provide valuable short-term prognostic information. At the current state of art, serial CRP measurements are instead not indicated to monitor disease course and plan hospital discharge in this setting.

ERAS approach (Enhanced Recovery After Surgery) is a multimodal, perioperative pathway designed to achieve early recovery after surgery. ERAS has shown documented efficacy in elective surgery, and the concept of “multimodal” and “multidisciplinary” approach seems still to be of higher importance than each single item within ERAS protocols. New perspectives include the use of ERAS in emergency surgery, where efficacy and safety on outcome have been documented, and flexibility of traditional items may add benefits for traditionally high-risk patients. Obstetric surgery, as well, may open wide horizons for future research, since extremely poor data are currently available, and ERAS benefits may translate even on the baby. Finally, the concept of “outcome” may be extended when considering the specific setting of cancer surgery, in which variables like cancer recurrence, early access to adjuvant therapies, and, finally, long-term survival are as important as the reduced perioperative complications. In this perspective, different items within ERAS protocols should be reinterpreted and eventually integrated towards “protective” techniques, to develop cancer-specific ERAS approaches keeping pace with the specific aims of oncologic surgery.

Background Patients undergoing pulmonary lobectomy carry a high risk of respiratory complications after surgery. The postoperative prophylactic treatment with helmet CPAP may prevent postoperative acute respiratory failure and improve the P(aO(2))/F(IO(2)). Methods We randomly allocated 50 subjects to receive continuous oxygen therapy (air-entrainment mask, F(IO(2)) 0.4) or 2 cycles of helmet CPAP for 120 min, alternating with analog oxygen therapy for 4 hours. Blood gas values were collected at admission to ICU, after 1, 3, 7, 9, 24 hours, and then in the thoracic ward after 48 hours and one week after surgery. We investigated the incidence of postoperative complications, mortality, and length of hospital stay. Results At the end of the second helmet CPAP treatment, the subjects had a significantly higher P(aO(2))/F(IO(2)), compared with the control group (366 ± 106 mm Hg vs 259 ± 60 mm Hg, P = .004), but the improvement in oxygenation did not continue beyond 24 hours. The postoperative preventive helmet CPAP treatment was associated with a significantly shorter hospital stay, in comparison to standard treatment (7 ± 4 d and 8 ± 13 d, respectively, P = .042). The number of minor or major postoperative complications was similar between the 2 groups. No difference in ICU readmission or mortality was observed. Conclusions The prophylactic use of helmet CPAP improved the P(aO(2))/F(IO(2)), but the oxygenation benefit was not lasting. In our study, helmet CPAP was a secure and well tolerated method in subjects who underwent pulmonary lobectomy. It might be safely applied whenever necessary.

Airtraq use by inexperienced personnel has been evaluated in simulator studies, but little is known about the learning process in real patients. This prospective study was designed to compare learning curves for laryngoscopy with the Airtraq or Macintosh laryngoscopes in patients under general anesthesia. Ten medical students with no prior experience in airway management were recruited on a voluntary basis and underwent training in Macintosh and Airtraq laryngoscopy. Patients with no difficult intubation criteria were enrolled after consent. Each student performed laryngoscopy with either device on ten consecutive patients. Success was defined as Cormack–Lehane grading ≤2. We also recorded subjective difficulty scores on an 11-point numerical rating scale. Learning curves were drawn using cumulative success rates and 95% confidence intervals calculated with bootstrap procedures. The mean (95% CI) success rates for the procedures were 86.0% (76.7–93.3%) for the Airtraq and 64.0% (52.0–75.0%) for the Macintosh laryngoscope. Differences in success rate were significant from the fourth attempt and were 22.0% (8.2–36.5%) after the tenth. Seven students achieved success rates ≥90% using the Airtraq, versus one using the Macintosh (P = 0.022). Median (25th–75th percentile) difficulty scores were 2 (1–4) and 4 (2–6), respectively (P

Keywords: Common indicators; policy responses; prescription painkillers dependence; monitoring; reporting

In this prospective, double-blind, randomized trial we compared 60 mg and 40 mg of 2% hyperbaric prilocaine with 60 mg of 2% plain prilocaine for spinal anesthesia in terms of sensory block onset in outpatients undergoing elective short-duration (60 minutes) surgery under spinal anesthesia.Ninety patients were enrolled and randomly allocated to receive 1 of the 3 treatments. Times to sensory and motor block onsets, time to the maximum sensory block level, readiness for surgery, time to first urinary voiding, time to Bromage's score 0, and side effects were registered blindly. A blinded observer also questioned patients about transient neurological symptoms 24 hours and 7 days after spinal anesthesia.Mean times to achieve a T10 level of sensory block were comparable in the 3 groups. However, 20% of patients receiving plain prilocaine did not achieve a T10 level. The 2 hyperbaric dosages (60 mg and 40 mg) showed significantly faster times to motor block onset (P = 0.0091, P = 0.0097), to the maximum sensory block level (P = 0.0297, P = 0.0183), to motor block offset (P = 0.0004, P0.0001), and to first urinary voiding (P = 0.0013, P = 0.0002, respectively) than did plain prilocaine. No major adverse reactions or transient neurological symptoms were observed in the study.Spinal anesthesia with 60 mg or 40 mg of 2% hyperbaric prilocaine is comparable to 60 mg of 2% plain prilocaine in terms of onset of sensory block at T10. The hyperbaric solution showed faster times to motor block onset and shorter duration of surgical block, suggesting its superiority for the ambulatory setting.

In the regional anesthesia field we assisted to an increasing study and use of ultrasound imaging for peripheral nerve blocks. This approach has been appreciated for good reliability in terms of clinical outcome of blocks and in terms of safety of the procedure. For this reason, ultrasound guidance is nearing to become the standard of care in regional anesthesia and for postoperative pain management. However, its role in invasive procedures in pain medicine is still discussed. The availability of other imaging techniques and lack of familiarization with ultrasonographic imaging are some of the reasons beneath this discrepancy. However, important steps are being made lately towards the development of safe, available and clinically efficient ultrasound guided techniques for many procedures in the pain medicine field.

In this prospective, randomised, observer-blinded study we evaluated whether ultrasound guidance can shorten the onset time of popliteal sciatic nerve block as compared to nerve stimulation with a multiple injection technique. Forty-four ASA I-III patients undergoing posterior popliteal sciatic nerve block with 20 ml of 0.75% ropivacaine were randomly allocated to nerve stimulation or ultrasound guided nerve block. A blinded observer recorded onset of sensory and motor blocks, success rates, the need for fentanyl intra-operatively, the requirement for general anaesthesia, procedure-related pain, patient satisfaction and side-effects. Onset times for sensory and motor blocks were comparable. The success rate was 100% for ultrasound guided vs 82% for nerve stimulation (p = 0.116). Ultrasound guidance reduced needle redirections (p = 0.01), were associated with less procedural pain (p = 0.002) and required less time to perform (p = 0.002). Ultrasound guidance reduced the time needed for block performance and procedural pain.

Background: The question of whether the dose, concentration or volume of a local anesthetic solution is the relevant determinant of the spread and quality of post-operative epidural analgesia is still open. In this prospective, randomized, double-blind study, we compared the effects of a large volume–low concentration with a small-volume–high-concentration lumbar epidural infusion of levobupivacaine. Methods: Seventy patients scheduled for total hip replacement were enrolled. After surgery, patients were randomly allocated to receive a continuous epidural infusion of levobupivacaine (10.5 mg/h) using either 0.125% levobupivacaine infused at 8.4 ml/h (low concentration group, n=35) or 0.75% levobupivacaine infused at 1.4 ml/h (high concentration group, n=35). We blindly recorded the degree of pain relief at rest and during movement every 8 h for the first two post-operative days, as well as hip flexion, motor block, rescue analgesic consumption and adverse events. Results: No difference in pain relief was observed between groups as estimated with the areas under the curve of the verbal Numerical Rating Scale for pain over time, both at rest and during movement. Similarly, there was no difference between groups in hip flexion degree, motor blockade and hemodynamic stability. Conclusions: Continuous lumbar epidural infusion of 0.75% levobupivacaine was as effective as continuous lumbar epidural infusion of 0.125% levobupivacaine, when administered at the same hourly dose of 10.5 mg, in achieving adequate analgesia both at rest and during movement, without differences in the incidence of hypotension and motor blockade.

Purpose: The aim of this prospective, randomised, blind study was to compare the evolution of spinal block produced with 50 mg lidocaine 10 mg/ml and 10 mg ropivacaine 5 mg/ml for outpatient knee arthroscopy. Methods: Thirty outpatients undergoing knee arthroscopy received 50 mg of lidocaine 10 mg/ml (n=15) or 10 mg of ropivacaine 5 mg/ml (n=15) intrathecally. The evolution of spinal block was recorded until home discharge, while the occurrence of transient neurologic symptoms (TNS) was evaluated through phone-call follow-ups. Results: The median onset time was 15 (10–21) min with lidocaine and 24 (11–37) min with ropivacaine (P=0.109). Spinal lidocaine resulted in a faster resolution of sensory block [148 (130–167) min vs. 188 (146–231) (P=0.022)], unassisted ambulation with crutches [176 (144–208) min vs. 240 (179–302) min (P=0.014)], and voiding [208 (163–254) min vs. 293 (242–343) min (P=0.001)] than ropivacaine. Recovery of motor function required 113 (95–131) min with lidocaine and 135 (87–183) with ropivacaine (P=0.219). Six lidocaine patients reported TNS (40%) as compared with no patient receiving ropivacaine (0%) (P=0.005). Conclusions: Spinal block produced with 10 mg ropivacaine 5 mg/ml is as effective as that produced by 50 mg of lidocaine 10 mg/ml. Recovery of unassisted ambulation and spontaneous voiding occurred earlier with lidocaine, but this was associated with a markedly higher incidence of TNS.

High success rates are attainable using state-of-the-art multiple electrical nerve stimulation, loss-of-resistance or fluoroscopic guidance techniques in most interventional acute and chronic pain techniques. Nevertheless, ultrasound (US) guidance for regional anesthesia and pain medicine offers compelling advantages in terms of precise location of anatomical structures, controlled needle advancement and local anesthetic deposition. Accurate models are needed to define criteria for the reproducibility of US examination and nerve block. Familiarization with US imaging is quickly becoming necessary as the next step in the evolution of interventional techniques for treating pain; consistent training by competent professionals is necessary to effectively leverage on the advantages of this technology.

Purpose: Levobupivacaine has been extensively evaluated for spinal anesthesia. Its pharmacologic properties are similar to those of bupivacaine, but differences in density between two commercially-available preparations of plain levobupivacaine might lead to different block profiles. We examined the characteristics of spinal anesthesia using the same dose of 0.5% and 0.75% plain levobupivacaine. Methods: In this randomized, controlled, double-blind clinical trial, 60 ASA I-III patients, scheduled for hip fracture surgery, were randomly allocated to receive spinal anesthesia with 15 mg of either 0.5% (group Levo-0.5), or 0.75% (group Levo-0.75) plain levobupivacaine. Onset time (primary outcome), sensory block height level by pinprick, motor block using a modified Bromage scale, and hemodynamic variables were recorded. Results: In group Levo-0.5 (n=29), surgical anesthesia was obtained within 15 (10–20) min, compared to 12 (7–21) min in group Levo-0.75 (n=31) (p=0.409). The highest sensory block level was T11 (T6–T12) in group Levo-0.5, and T10 (T8–T12) in group Levo-0.75 (p=0.759). Mean duration of anesthesia was 285 (224–303) min in group Levo-0.5, and 318 (243–375) min in group Levo-0.75 (p=0.117). The groups were similar in regards to the number of failed blocks requiring general anesthesia, and the number of patients requiring vasopressors. Conclusions: In this population of elderly patients, spinal anesthesia with 15 mg of either 0.5% or 0.75% plain levobupivacaine resulted in similar onset of pharmacological actions, and outcomes. Potential differences in baricity did not appear to be clinically relevant in this setting.

Purpose The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen, proparacetamol. Materials and Methods Fifty American Society of Anesthesiology (ASA) physical status I-II patients, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy, were investigated in a prospective, randomized, double-blind manner. After local infiltration with 1% mepivacaine, patients were randomly allocated to receive intravenous (IV) administration of either 40 mg of parecoxib (n = 25) or 2 g of proparacetamol (n = 25) 15 min before discontinuation of total IV anaesthesia with propofol and remifentanil. A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit (PACU) at 10, 20, and 30 min after PACU admission, and every 1 h thereafter for the first 6 postoperative h. Results The area under the curve of VAS (AUCVAS) calculated during the study period was 669 (28 - 1901) cm·min in the proparacetamol group and 635 (26 - 1413) cm·min in the parecoxib group (p = 0.34). Rescue morphine analgesia was required by 14 patients (56%) in the proparacetamol group and 12 patients (48%) in the parecoxib (p ≥ 0.05), while mean morphine consumption was 5 - 3.5 mg and 5 - 2.0 mg in the proparacetamol groups and parecoxib, respectively (p ≥ 0.05). No differences in the incidence of side effects were recorded between the 2 groups. Patient satisfaction was similarly high in both groups, and all patients were uneventfully discharged 24 h after surgery. Conclusion In patients undergoing endoscopic nasal surgery, prior infiltration with local anaesthetics, parecoxib administered before discontinuing general anaesthetic, is not superior to proparacetamol in treating early postoperative pain.

Objective. This study aims to assess long-term follow-up of efficacy and quality of life for 34 geriatric patients (10 men, 24 women, mean age 72.3 ± 11.6 years) with intrathecal (IT) drug delivery systems (IDDS), implanted between 1994 and 2002, for the treatment of severe noncancer chronic pain. Methods. Patients equal to or older than 64 years, who had no pain relief after administration of a placebo injection (subcutaneous saline), and who responded positively to an IT trial (morphine and bupivacaine at low doses) with pain relief greater 70% without intolerable adverse effects were included into our study. Clinical assessment forms and questionnaires assessing pain intensity, adverse events, complications, concommitent use of analgesics, and doses of IT drugs administered were filled out by our patients prior to and after IT drug delivery implantation. Results. Pain intensity was substantially reduced (60%) at three-month follow-up after commencing IT therapy and was consistently reduced at 48-month follow-up. The mean visual analog scale (VAS) value decreased from 8.09 (± 1.25) before implantation to 1.68 (± 0.63) after implantation at 48-month follow-up. This benefit, at 48 months, was achieved using mean low doses of IT morphine and bupivacaine, 1.03 ± 0.61 mg and 1.15 ± 0.58 mg, respectively. Only two out of 34 patients (5.9%) had complications related to the implantation procedure, itself. Side-effects of therapy were reported by 50% of the patients, the most frequent being constipation (34.4%), drowsiness (21.9%), nausea (21.9%), and urinary retention (18.8%). No side-effects of therapy resulted in removal of the IDDS. Conclusion. The use of IT drug delivery through IDDS for the treatment of non-cancer- and cancer-related pain in geriatric patients is successful.

Perineural catheter infection is a rare but potentially dramatic complication of continuous peripheral nerve block. Different risk factors have been identified and the incidence of infection is increased in trauma victims, intensive care unit patients, immunodeficient individuals, and diabetic patients. Also, postoperative hyperglycemia, the absence of antibiotic prophylaxis, and catheter lasting more than 48 hours seem to be associated with a greater risk of infection. Skin disinfection and a strict aseptic technique during catheter placement are fundamental. The use of micropore filters, antiseptic dressings, catheter tunneling, and aseptic preparation of the infused drug has all been hypothesized to reduce infection rate, but the existing evidence is conflicting. Infection is a rare complication of continuous peripheral nerve blocks. Severe and even fatal cases have been reported, even if morbidity is generally very low. The identification of high risk patients and adoption of preventive measures might reduce the incidence of this complication.

High interindividual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain, and single nucleotide polymorphisms (SNPs) within opioid receptor μ 1 ( OPRM1 ), catechol-O-methyltransferase ( COMT ), uridine diphosphate glucose-glucuronosyltransferase-2B7, and estrogen receptor ( ESR1 ) gene loci to elucidate genetic prediction of opioid consumption. We analyzed 20 SNPs in 201 unrelated Caucasian patients who underwent abdominal surgery and who were receiving postoperative patient-controlled analgesia-administered morphine. Morphine consumption and pain intensity were dependent variables; age and sex were covariates. A haplotype of 7 SNPs in OPRM1 showed significant additive effects on opioid consumption ( P = .007); a linear regression model including age and 9 SNPs in ESR1 , OPRM1 , and COMT explained the highest proportion of variance of morphine consumption (10.7%; P = .001). The minimal model including 3 SNPs in ESR1 , OPRM1 , and COMT explained 5% of variance ( P = .007). We found a significant interaction between rs4680 in COMT and rs4986936 in ESR1 ( P = .007) on opioid consumption. SNPs rs677830 and rs540825 of OPRM1 and rs9340799 of ESR1 were nominally associated with pain Numeric Rating Scale scores. Combinations of genetic variants within OPRM1 , COMT , and ESR1 better explain variability in morphine consumption than single genetic variants. Our results contribute to the development of genetic markers and statistical models for future diagnostic tools for opioid consumption/efficacy. Perspective This article presents the efforts dedicated to detect correlations between the genetic polymorphisms and the clinical morphine effect self-administered by patients using a patient-controlled analgesia pump after major surgery. The clinical effect is expressed in terms of morphine consumption and pain scores. Registered on ClinicalTrials.gov NCT01233752.

Poor acute pain control and inflammation are important risk factors for Persistent Postsurgical Pain (PPSP). The aim of the study is to investigate, in the context of a prospective cohort of patients undergoing hernia repair, potential risk factors for PPSP. Data about BMI, anxious-depressive disorders, neutrophil-tolymphocyte ratio (NLR), proinflammatory medical comorbidities were collected. An analysis for correlation between comorbidities and PPSP was performed in those patients experiencing chronic pain at 3 months after surgery. Tramadol resulted less effective in pain at movement in patients with a proinflammatory status. Preoperative hypertension and NLR > 4 were correlated with PPSP intensity. Regional anesthesia was significantly protective on PPSP when associated with ketorolac. Patients with pain at 1 month were significantly more prone to develop PPSP at 3 months. NSAIDs or weak opioids are equally effective on acute pain and on PPSP development after IHR, but Ketorolac has better profile in patients with inflammatory background or undergoing regional anesthesia. Drug choice should be based on their potential side effects, patient’s profile (comorbidities, preoperative inflammation, and hypertension), and type of anesthesia. Close monitoring is necessary to early detect pain conditions more prone to progress to a chronic syndrome.

This study compared the performance of forehead reflectance and conventional pulse oximetry (SpO(2)) in mechanically ventilated, anesthetized patients undergoing major abdominal surgery with either laparoscopic or laparotomic techniques.SpO(2) was continuously measured both with a forehead reflectance and a conventional digit sensor in 20 ASA physical status I-III, anesthetized patients undergoing either a laparotomic (group Laparotomy, n = 10) or laparoscopic (group Laparoscopy, n = 10) major abdominal surgery. SpO(2) values measured with the two sensors were continuously recorded at 10-second intervals during the entire procedure, and then analyzed for consistency.In group Laparotomy finger and forehead readings remained consistently similar during the study period; on the contrary, in group Laparoscopy forehead SpO(2) readings showed a much wider variability. The mean (95% Confidence Intervals) difference between finger and forehead SpO(2) readings was 2.0% (-1.3% to +6.0%) in group Laparotomy and 2.5% (-3.5% to +8.4%) in group Laparoscopy (p = 0.001); however, in group Laparoscopy the mean difference between digit and forehead SpO(2) values increased from 0.2% (CI(95): -2.1% to +2.5%) during the first hour to 4.5% (CI(95): -2.5% to +11-5%) in the second hour (p = 0.0005), and 3.1% (CI(95): -2.4% to + 8.6%) in the third hour of surgery (p = 0.0005). Clinically relevant desaturation (decrease of SpO(2)89% foror =30 s) detected with the forehead sensor in the Laparoscopy group was significantly more frequent and longer lasting than with conventional digit sensor. No differences were observed in group Laparotomy.Forehead reflectance oximetry is as accurate as conventional digit based oximetry in mechanically ventilated patients undergoing laparotomic surgery in the supine position, but is significantly influenced by patient positioning and pneumoperitoneum during laparoscopic surgery.

Background The aim of this prospective, randomized, double-blind, placebo-controlled study was to evaluate the efficacy of phrenic nerve infiltration with ropivacaine 0.2% on the incidence and severity of ipsilateral shoulder pain after thoracotomy in patients receiving continuous thoracic epidural analgesia. Methods Fifty ASA physical status II-III patients, receiving thoracic epidural analgesia for post-thoracotomy pain, were randomly allocated to receive infiltration of the ipsilateral phrenic nerve with either ropivacaine 0.2% 10 mL (ropivacaine, n = 25), or saline 0.9% (control, n = 25) just before lung expansion and chest closure. A blinded observer recorded the incidence and severity of ipsilateral shoulder pain 6, 12, 24, 36 and 48 h after surgery. Postoperative respiratory function was also evaluated with blood gas analyses. Results The cumulative incidences of ipsilateral shoulder pain during the first 24 h after surgery were 8/25 in the ropivacaine and 16/25 in the control groups (P = 0.047), with median (range) onset times for shoulder pain of 2 (2-24) h with ropivacaine and 0.5 (0.5-24) h in controls (P = 0.005). No differences were reported on the second postoperative day. The areas under the curves of the amount of pain over time were 0 (0-2760) mm h for the ropivacaine and 350 (0-1900) mm h for the control groups (P = 0.06). Postoperatively, similar reductions in indices of oxygenation were observed in both groups. Conclusions Phrenic nerve infiltration with ropivacaine 0.2% 10 mL reduced the incidence and delayed the onset of ipsilateral shoulder pain during the first 24 h after open lung resection, with no clinically relevant effects on respiratory function.

Background We tested the hypothesis that ultrasound guidance may reduce the minimum effective anaesthetic volume (MEAV50) of ropivacaine 0.5% required to block the femoral nerve compared with nerve stimulation guidance. Methods After standard premedication and sciatic nerve block were given, 60 patients undergoing knee arthroscopy were randomly allocated to receive a femoral nerve block with ropivacaine 0.5% using either nerve stimulation (group NS, n = 30) or ultrasound (group US, n = 30) guidance. The volume of the injected solution was varied for consecutive patients based on an up-and-down staircase method according to the response of the previous patient. The initial volume was 12 ml. A double-blinded observer evaluated the occurrence of complete loss of pinprick sensation in the femoral nerve distribution, with concomitant block of the quadriceps muscle: positive or negative responses within 30 min after the injection determined a 3 ml decrease or increase for the next patient, respectively. Results The mean ( sd ) MEAV50 for femoral nerve block was 15 (4) ml (95% CI, 7–23 ml) in group US and 26 (4) ml (95% CI, 19–33 ml) in group NS (P = 0.002). The effective dose in 95% of cases (ED95) calculated with probit transformation and logistic regression analysis was 22 ml (95% CI, 13–36 ml) in group US, and 41 ml (95% CI, fs 24–66 ml) in group NS. Conclusions Ultrasound guidance provided a 42% reduction in the MEAV of ropivacaine 0.5% required to block the femoral nerve as compared with the nerve stimulation guidance.

In this prospective, randomized, double-blind study we tested the hypothesis that 50 mg of 1% preservative-free 2-chloroprocaine would provide a faster resolution of spinal block than the same dose of 1% plain lidocaine.After IV midazolam premedication (0.03 mg/kg), 30 ASA physical status I-II outpatients undergoing knee arthroscopy were randomly allocated to receive 50 mg of either 1% plain lidocaine (n = 15) or 1% preservative-free plain chloroprocaine (n = 15). A blinded observer recorded the evolution of sensory (loss of pinprick sensation) and motor (modified Bromage scale) block until complete regression, as well as times to unassisted ambulation and voiding. A telephone call follow-up was performed 24 h and 7 days after surgery.Two chloroprocaine patients (13%) and one lidocaine patient (7%) required fentanyl supplementation (100 microg IV) (P = 0.99) intraoperatively, but no patient required general anesthesia to complete surgery. Median (range) times for recovery of sensory and motor function, and unassisted ambulation were faster with 2-chloroprocaine [95 (68-170) min; 60 (45-120) min; and 103 (70-191) min] than lidocaine [120 (80-175) min; 100 (60-140) min; and 152 (100-185) min] (P = 0.019, P = 0.0005, and P = 0.003, respectively). No differences in first voiding were reported between chloroprocaine [180 (100-354) min] and lidocaine patients [190 (148-340) min] (P = 0.191). Transient neurological symptoms were reported in five lidocaine patients (33%) but no chloroprocaine patients (0%) (P = 0.042).Intrathecal injection of 50 mg of preservative-free 2-chloroprocaine 1% resulted in quicker recovery of sensory/motor function, and unassisted ambulation, and fewer incidences of transient neurologic symptoms than the same dose of 1% lidocaine.

Aim: Checklists may improve management of patients in different settings. However, no studies have been conducted to investigate the use of this tool to improve inpatient pain control. This study, conducted in Italy, aims to describe the experience, in terms of pain control, of the widespread introduction of a checklist for pain control in oncological patients, according to current Italian legislation. Materials & methods: In total, 92 Italian centers were randomly assigned to the use of the 38Checkpain to monitor pain management or to continue their standard practice without the use of this tool. Results: The 38Checkpain improved the control of pain compared with centers who did not use this tool. Conclusion: Overall, the findings of this study suggest that the application of the 38Checkpain may help improve control of pain of hospitalized oncological patients.

Inflammatory response is one of the key components of pain perception. Continuous infusion (CWI) of local anesthetics has been shown to be effective in controlling pain and reducing postoperative morphine consumption, but the effect of adding a potent anti-inflammatory drug (such as a steroid) has never been addressed. In our study, we want to investigate the effect of CWI with local anesthetic + methylprednisolone on acute and persistent pain, correlating clinical data with biomarkers of inflammation and genetic background. After approval by their institutional review board, three hospitals will enroll 120 patients undergoing major abdominal surgery in a randomized, double-blind, phase III study. After a 24-h CWI of ropivacaine 0.2 % + methylprednisolone 1 mg/kg, patients will be randomly assigned to receive either ropivacaine + steroid or placebo for the next 24 h. Then, patient-controlled CWI with only ropivacaine 0.2 % or placebo (according to the group of randomization) is planned after 48 h up to 7 days (bolus 10 ml, lock-out 1 h, maximum dose of 40 ml in 4 h). Morphine equivalent consumption up to 7 days will be analyzed, together with any catheter- or drug-related side effect. Persistent post-surgical pain (PPSP) incidence will also be investigated. Our primary endpoint is analgesic consumption in the first 7 days after surgery; we will evaluate, as secondary endpoints, any catheter- or drug-related side effect, genotype/phenotype correlations between some polymorphisms and postoperative outcome in terms of morphine consumption, development of the inflammatory response, and incidence of PPSP. Finally, we will collect, in a subgroup of patients, wound exudate samples by micro-dialysis, blood samples, and urine samples up to 72 h to investigate local and systemic inflammation and oxidative stress. This is a phase III trial to evaluate the safety and efficacy of wound infusion with steroid and local anesthetic. The study is aimed also to evaluate how long this infusion has to be maintained in order to maximize effectiveness. Our data are intended to quantify the amount of ropivacaine and methylprednisolone needed by patients undergoing major abdominal surgery, to be stored in a new nanotechnology device for sustained pain treatment after surgery. We also aim to clarify the roles of inflammatory response, oxidative stress, and genetic background on postoperative and persistent pain after major abdominal surgery. The trial was registered on ClinicalTrials.gov ( NCT02002663 ) on 24 Oct. 2013.

Chronic pain is a highly disabling condition, which can significantly reduce patients' quality of life. Prevalence of moderate and severe chronic pain is high in the general population, and it increases significantly in patients with advanced cancer and older than 65 years. Guidelines for the management of chronic pain recommend opioids for the treatment of moderate-to-severe pain in patients whose pain is not responsive to initial therapies with paracetamol and/or nonsteroidal anti-inflammatory drugs. Despite their analgesic efficacy being well recognized, adverse events can affect daily functioning and patient quality of life. Opioid-induced constipation (OIC) occurs in 40% of opioid-treated patients. Laxatives are the most common drugs used to prevent and treat OIC. Laxatives do not address the underlying mechanisms of OIC; for this reason, they are not really effective in OIC treatment. Naloxone is an opioid receptor antagonist with low systemic bioavailability. When administered orally, naloxone antagonizes the opioid receptors in the gut wall, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influence on the central-mediated analgesic effect of the opioids. A prolonged-release formulation consisting of oxycodone and naloxone in a 2:1 ratio was developed trying to reduce the incidence of OIC maintaining the analgesic effect compared with use of the sole oxycodone. This review includes evidence related to use of oxycodone and naloxone in the long-term management of chronic non-cancer pain and OIC.

To evaluate the effects of adding 50 microg clonidine to 150 mg ropivacaine for superficial cervical plexus block in patients undergoing elective carotid endarterectomy (TEA).Randomized, double-blind study.Departments of Anesthesia and Vascular Surgery of a university hospital.40 ASA physical status II and III patients undergoing elective TEA during superficial cervical plexus block.Superficial cervical plexus block was placed using 20 mL of 0.75% ropivacaine alone (Ropi group, n = 20) or with the addition of 50 microg clonidine (Ropi-Clonidine group, n = 20). If required, analgesic supplementation was given with local infiltration with 1% lidocaine and intravenous fentanyl (50-microg boluses). Nerve block profile, need for intraoperative analgesic supplementation, and time to first analgesic request were recorded.Median (range) onset time was 10 minutes (5-25 min) in the Ropi group and 5 minutes (5-20 min) in the Ropi-Clonidine group (P0.05). Intraoperative consumption of both 1% lidocaine and fentanyl was higher in patients of the Ropi group (15 mL [0-25 mL] and 250 microg [50-300 microg]) than in patients of the Ropi-Clonidine group (8 mL [0-20 mL] and 0 microg [0-150 microg]; P0.05 and P0.05, respectively). First postoperative analgesic request occurred after 17 hours (10-24 hrs) in the Ropi group and 20 hours (10-24 hrs) in the Ropi-Clonidine group (P0.05).Adding 50 microg clonidine to 150 mg ropivacaine for superficial cervical plexus block shortened the onset time and improved the quality of surgical anesthesia in patients undergoing elective TEA.

Background: We prospectively evaluated direct analgesia-related costs of continuous sciatic nerve block using either a stimulating or conventional catheter after hallux valgus repair. Methods: The perineural catheter was inserted through a stimulating introducer either blindly (group Conventional, n= 38) or while stimulating via the catheter (group Stimulating, n= 38). Nerve block was induced with 25 ml of mepivacaine 15 mg/ml, and was followed 3 h later by a patient-controlled infusion of ropivacaine 2 mg/ml (basal infusion: 3 ml/h; incremental dose: 5 ml; lock-out time: 30 min). Rescue tramadol [100 mg intravenous (i.v.)] was given if required. Local anesthetic consumption, need for rescue tramadol and post-operative nausea and vomiting (PONV) treatment, and patient’s satisfaction were recorded during first 24-h infusion. Cost calculations were based on the acquisition cost of drugs and devices. Results: Both techniques were similarly effective, but local anesthetic consumption and need for rescue analgesics were lower in the Stimulating group [respectively, 120 vs. 153 ml (P= 0.004) and 21% vs. 60% (P= 0.001)]. The analgesia-related costs for 24 h were similar when 100-ml bags of ropivacaine 2 mg/ml were used (66 € vs. 67 €; P= 0.26). When 200-ml bags of ropivacaine were used, the analgesia-related costs were higher in the Stimulating group than the Conventional group (75 € vs. 55 €; P= 0.0005). Conclusions: Direct costs of continuous sciatic nerve block ranged from 55 to 75 €. Stimulating catheters reduced local anesthetic consumption and need for rescue analgesics. This was only cost effective when 100-ml bags of 2 mg/ml ropivacaine were used, while the cheapest combination was the use of conventional catheters and 200-ml bags of ropivacaine.

Study objective To evaluate the efficacy of three different concentrations of ropivacaine (0.5%, 0.75%, and 1%) together with a single concentration of hyaluronidase administered for peribulbar block. Design Prospective, randomized, double-blind study. Setting Anesthesia department of a university teaching hospital. Patients 68 ASA physical status I, II, and III patients undergoing elective cataract surgery. Interventions Patients were randomly allocated to receive peribulbar block with 6.5 mL of either 0.5% (Group Ropi-5; n=22), 0.75% (Group Ropi-7.5; n=22), or 1% ropivacaine (Group Ropi-10; n=24). In all patients, 0.5 mL of hyaluronidase was added to the local anesthetic solution. Measurements and main results A larger proportion of patients in Groups Ropi-7.5 (82%) and Ropi-10 (83%) showed complete motor block 15 minutes after injection compared with Group Ropi-5 (55%; p = 0.05, and p = 0.03, respectively). Hypotension (reduction of systolic blood pressure by 30% or more from baseline) was observed in two Group Ropi-5 patients (9%), and two Group Ropi-7.5 patients (9%; p = 0.31), whereas bradycardia (reduction in heart rate ≤ 50 bpm) was observed in one Group Ropi-5 patient (4%), and three Group Ropi-10 patients (12%; p = 0.18). Seven hours after surgery, a smaller proportion of Group Ropi-10 patients (64%) showed complete recovery of sensory function as compared with both Group Ropi-5 (94%) and Group Ropi-7.5 (90%; p = 0.03 and p = 0.03, respectively). Complete recovery of motor function 1 hour after surgery was more frequent in Group Ropi-5 (37%) than in Group Ropi-7.5 (5%) or Group Ropi-10 (9%; p = 0.05 and p = 0.05, respectively); however, no other differences in recovery of motor function were observed at any other observation times, with complete recovery in all patients 7 hours after surgery. Conclusions While confirming that ropivacaine is a good option for peribulbar anesthesia, this study demonstrated that the use of 0.75% or 1% concentrations are preferred in that they produce quick and deep sensory and motor block of the operated eye. If recovery of normal motor function is important after surgery, the 0.75% concentration probably represents the best compromise.

UNLABELLED We compared the onset time and quality of interscalene brachial plexus block produced with levobupivacaine and ropivacaine in 50 patients undergoing open shoulder surgery randomly allocated to receive 30 mL of 0.5% levobupivacaine (n = 25) or 0.5% ropivacaine (n = 25) injected through a 20-gauge catheter placed into the interscalene sheath using a 18-gauge insulated and stimulating Tuohy introducer. The block was also prolonged after surgery using a patient-controlled interscalene analgesia with 0.125% levobupivacaine or 0.2% ropivacaine, respectively (basal infusion rate, 6 mL/h; bolus, 2 mL; lockout period, 15 min; maximum boluses per hour, three). Three patients (two with levobupivacaine [8%] and one with ropivacaine [4%]) failed to achieve surgical block within 45 min after the injection and were excluded. The onset time of surgical block was 20 min (10-40 min) with levobupivacaine and 20 min (5-45 min) with ropivacaine (P = 0.53). Rescue intraoperative analgesia (0.1 mg of fentanyl IV) was required in eight patients in each group (34%) (P = 0.99). Forty-two patients completed the 24-h postoperative infusion (22 with levobupivacaine and 20 with ropivacaine). Postoperative analgesia was similarly effective in both groups. Total consumption of local anesthetic infused during the first 24 h was 147 mL (144-196 mL) with levobupivacaine and 162 mL (144-248 mL) with ropivacaine (P = 0.019), with a ratio between boluses received and requested of 0.8 (0.4-1.0) and 0.7 (0.4-1.0), respectively (P = 0.004). The degree of motor block of the operated limb was deeper with levobupivacaine than ropivacaine when starting postoperative analgesia; however, no further differences in degree of motor function were observed between the two groups. We conclude that 30 mL of levobupivacaine 0.5% induces an interscalene brachial plexus anesthesia of similar onset and intensity as the one produced by the same volume and concentration of ropivacaine. Postoperative interscalene analgesia with 0.125% levobupivacaine results in similar pain relief and recovery of motor function with less volume of local anesthetic than with 0.2% ropivacaine. IMPLICATIONS This prospective, randomized, double-blinded study demonstrates that 30 mL of 0.5% levobupivacaine produces an interscalene brachial plexus block of similar onset and quality as the one produced by the same volume of 0.5% ropivacaine. When prolonging the block after surgery, 0.125% levobupivacaine provides adequate pain relief and recovery of motor function after open shoulder surgery, with less volume infused during the first 24 h after surgery than 0.2% ropivacaine.

Summary The efficacy of surgical anaesthesia and postoperative analgesia after elective orthopaedic foot surgery was evaluated in 200 healthy patients, randomly allocated to receive either a bilateral spinal anaesthesia (group BSA, n = 50), a unilateral spinal anaesthesia (group USA, n = 50), or a combined sciatic-femoral nerve block performed with 2% mepivacaine (group SFM, n = 50) or 0.75% ropivacaine (group SFR, n = 50). Similar duration of surgery was reported in the four groups (median 50 min, range 20–90 min), without differences in times of thigh tourniquet. Surgeon satisfaction was 92% in group SFM and 90% in group SFR, 94% in group BSA and 94% in group USA ( P = 0.18). Tourniquet pain during surgery was reported in two SFM patients and three SFR patients, while two patients in each group required anaesthetic implementation. No urinary retention was reported in SFM and SFR groups, but seven BSA patients (14%) and one USA patient (2%) required bladder catheterization ( P = 0.005). Postoperative analgesia was longer in group SFR (13.4 h) than in the SFM (4.6 h), BSA (3.1 h), and USA (3.2 h) groups ( P = 0.0005), with reduced analgesic consumption ( P = 0.0005). When providing anaesthesia for foot and ankle procedures, the combination of sciatic and femoral nerve blocks is as effective and safe as spinal anaesthesia with less urinary retention. Longer postoperative analgesia is provided by ropivacaine than mepivacaine.

Roberto Casale,1,2 Maria Di Matteo,3,7 Cristina E Minella,4,7 Guido Fanelli,5,7 Massimo Allegri4,6,71Department of Clinical Neurophysiology and Pain Rehabilitation Unit, Foundation Salvatore Maugeri, IRCCS, Pavia, 2EFIC Montescano School, Montescano, 3Anesthesia and Intensive Care I, 4Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, 5Department of Anesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, 6Department of Clinical, Surgical, Diagnostic and Pediatric Science, University of Pavia, Pavia, 7Study In Multidisciplinary Pain Research Group, Parma, ItalyAbstract: Post-herpetic neuralgia (PHN) is neuropathic pain persisting after an acute episode of herpes zoster, and is associated with severe pain and sensory abnormalities that adversely affect the patient's quality of life and increase health care costs. Up to 83% of patients with PHN describe localized neuropathic pain, defined as “a type of neuropathic pain characterized by consistent and circumscribed area(s) of maximum pain”. Topical treatments have been suggested as a first-line treatment for localized neuropathic pain. Use of 5% lidocaine medicated plaster could reduce abnormal nervous peripheral discharge and via the plaster could have a “protective” function in the affected area. It has been suggested that use of this plaster could reduce pain as well as the size of the painful area. To evaluate this possible outcome, we retrospectively reviewed eight patients with PHN, treated using 5% lidocaine medicated plaster. During a follow-up period of 3 months, we observed good pain relief, which was associated with a 46% reduction in size of the painful area after one month (from 236.38±140.34 cm2 to 128.80±95.7 cm2) and a 66% reduction after 3 months (81.38±59.19 cm2). Our study cohort was composed mainly of elderly patients taking multiple drugs to treat comorbidities, who have a high risk of drug–drug interactions. Such patients benefit greatly from topical treatment of PHN. Our observations confirm the effectiveness of lidocaine plasters in the treatment of PHN, indicating that 5% lidocaine medicated plaster could reduce the size of the painful area. This last observation has to be confirmed and the mechanisms clarified in appropriate larger randomized controlled trials.Keywords: localized neuropathic pain, topical treatment, chronic pain, drug–drug interactions, patient's outcome

Pain is a common symptom in orthopedic patients, but is managed sub-optimally, partly due to scarce opioid use in severe cases. The aim of the Orthopedic Instant Pain Survey (POIS) was to evaluate changes in pain management in Italian orthopedic practice 2 years after a legislative change (Law 38/2010) simplifying opioid access for pain control. A web-based survey on the knowledge of this law and trends observed in clinical practice for severe pain treatment was administered to 143 Italian orthopedic specialists. In total, 101 (70%) respondents showed a high level of knowledge. Nevertheless, 54.5% stated that they do not use opioids for severe osteo-articular pain management. Main barriers to opioid use are fear of adverse events (61.4%), especially nausea/vomiting and constipation, and patient resistance (29.7%). A modest knowledge of pain classification was also demonstrated. Opioid use remains very limited in Italian orthopedic practice. Physicians’ fear of side effects showed poor knowledge of strategies for effective management of opioid-related adverse events, such as combined oral prolonged-release oxycodone/naloxone. Continuing educational programs could improve delivery of evidence-based pain management.

Purpose: To compare unilateral and conventional bilateral bupivacaine spinal block in outpatients undergoing knee arthroscopy. Methods: One hundred healthy, premedicated patients randomly received conventional bilateral (n=50) or unilateral (n=50) spinal anesthesia with 8 mg hyperbaric bupivacaine 0.5%. A lateral decubitus position after spinal injection was maintained in unilateral group for 15 min. Times from spinal injection to readiness for surgery, block resolution, and home discharge were recorded. Results: Three patients in each group were excluded due to failed block. Readiness for surgery required 13 min (5 – 25 min) with bilateral and 16 min (15 – 30) with unilateral spinal block (P=0.0005). Sensory and motor blocks on the operated limb were T9 (T12 – T2) with a Bromage score 0/1/2/3: 0/2/0/45 in the unilateral group and T7 (T12 – T1) with Bromage score 0/1/2/3: 4/1/6/36 with bilateral block (P=0.026 andP=0.016, respectively). Vasopressor was required only in five bilateral patients (P=0.02). Two segment regression of sensory level and home discharge required 81±25 min and 281±83 min with bilateral block, and 99±28 min and 264±95 min with unilateral block (P=0.002 andP=0.90, respectively). Conclusion: Seeking unilateral distribution of spinal anesthesia provided more profound and longer lasting block in the operated limb, less cardiovascular effects, and similar home discharge compared with bilateral spinal anesthesia, with only a slight delay in preparation time.

To evaluate the effects of adding low concentration of fentanyl to 0.2% ropivacaine when providing patient-controlled epidural analgesia (PCEA) outside the Post-Anesthesia Care Unit.Prospective, randomized, double-blind study.Inpatients at a University Department of Anesthesia.32 ASA physical status I, II, and III patients, who were scheduled for elective major abdominal surgery, including bowel resection, hepatic resection, and pancreaticoduodenectomy.Patients received standard general/epidural anesthesia. After surgery patients were randomly allocated in a double-blind fashion to receive PCEA with either 0.2% ropivacaine (n = 16) or 0.2% ropivacaine/2 microg/mL fentanyl (n = 16) [background infusion ranging between 4 and 6 mL/hr, with 1.5-mL incremental doses and a 20-min lock-out time]. Dynamic pain during coughing, sedation, pulse oxymetry, hemodynamic variables, and motor block were evaluated at 1, 6, 12, 24, and 48 hours after the end of surgery by a blinded observer. Occurrence of untoward events, including nausea, vomiting, pruritus, need for supplemental oxygen (for SpO(2)90%), and respiratory complications, as well as total consumption of PCEA solution and incremental doses given to the patient were also recorded.No differences in pain relief, motor block, degree of sedation, recovery of gastrointestinal motility, and other side effects were observed between the two groups. Patients receiving 0.2% ropivacaine alone requested far more incremental doses (23 doses [0-60] vs. 5 doses [0-25]) (p = 0.006) and needed far more analgesic solution (230 mL [140-282] vs. 204 [130-228]) (p = 0.003) than patients receiving the ropivacaine/fentanyl mixture. Peripheral oxygen saturation was lower at 12, 24, and 48 hours during ropivacaine/fentanyl infusion than in patients receiving ropivacaine alone (12 h: 91% +/- 2% vs. 95% +/- 2%, p0.006; 24 h: 93% +/- 1% vs. 96% +/- 2%, p = 0.003; 48 h: 92% +/- 1.8% vs. 96% +/- 1%, p = 0.004).A thoracic epidural infusion of 0.2% ropivacaine, with or without fentanyl, provided effective pain relief in most patients with a very low degree of motor blockade. Adding 2 microg/ml fentanyl to 0.2% ropivacaine reduced total consumption of local anesthetic solution and need for incremental doses, but did not provide clinically relevant advantages in quality of pain relief and incidence of motor block, leading to a significant decrease in peripheral SpO(2), lasting up to 48 hours after surgery.