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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

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.

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 (

Acute and chronic pain have an important socio-economical impact. In order to help physicians to choose the appropriate drug, especially for cancer pain, in 1986 WHO has developed a three-step analgesic “ladder” for cancer pain relief in adults. Later it has also been used for acute pain and chronic non-cancer pain. In step I nonsteroidal anti-inflammatory drugs (NSAIDs) are considered with or without adjuvants, in step II the use of weak opioids for mild-moderate pain, with or without NSAIDs and adjuvant, is suggested, while the step III is reserved to strong opioids for moderate-severe pain with or without non-opioids or adjuvants. In the last two decades, a better pathophysiology knowledge has improved pain management shifting our view from the pain ladder to a modern pain pyramid, in which drugs are selected not only on the basis of pain intensity, but mainly according to mechanisms underlying pain, including peripheral and spinal sensitization which is the main trigger of chronic pain. The best pharmacological approach has become multimodal, in which drugs belonging to different steps should be combined, matching the mechanisms of action with the type of pain. An important corollary of combining analgesic drugs with different mechanism of action is that proper matching achieves the same effect with lower doses, better outcome and fewer adverse effects. In this new perspective, fixed-dose pharmaceutical combinations of different drugs are very useful to fulfil pharmacodynamics, pharmacokinetics and adherence criteria, enriching the pain pyramid of half-steps between the first and second step and between the second and third step. Hence, a new fixed combination of a NSAID with peripheral and central anti-infilammatory activities, such as dexketoprofen, and a weak opioid, such as tramadol, with double analgesic activity in the spinal cord as an opioid and, at the same time, on the descending modulatory pathways, is expected to cover a wide range of acute and recurrent painful conditions, ranging from nociceptive inflammatory pain to neuropathic pain of moderate/severe intensity. In this review we evaluate the rationale that justifies its use as new class of pharmacological modality to treat pain accordingly also to a more update view of WHO pain ladder. (www.actabiomedica.it)

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.

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

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

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.

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.

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

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.

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.

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.

Regional anesthesia (RA) is associated with many advantages, but side effects also occur. Several registries were developed to investigate such complications in many countries, which produced conflicting results. In consideration of the ongoing evolution and improvements in RA, and its widespread diffusion in Italy in the last decade (with increasing experience by anesthesiologists), a reappraisal of the incidence and the characteristics of major complications are useful to improve patient's safety.A web-based prospective registry was developed in Italy with: 1) quarterly report of total anesthetic acts and RA procedures performed; and 2) voluntary registration of complications on dedicated forms. We evaluated incidence of complications, describing their characteristics and outcomes.Participants (N.=17 hospitals) registered 117,182 procedures, including 63,692 with RA (54.3%, both as primary anesthetic technique and for postoperative analgesia). A total of 34,147 neuraxial blocks (4954 epidurals/CSE, 29,193 subarachnoid blocks) and 29,545 peripheral (single shot and continuous) blocks were registered. Total incidence of complication was 4.6/10.000; incidence was 4.1/10,000 for central blocks and 5.1/10,000 for peripheral blocks, long-term neurologic deficit (at 6 months) was observed after an epidural abscess, while other complications did not lead to any long-term adverse outcomes. No hemorrhagic events or other infections have occurred. Incidence of major complications was 0.07/1000, while minor complications presented in 0.38/1000 cases.We confirmed RA as generally safe, but monitoring and diagnosis, together with further research efforts, are needed to improve patients' care and clarify potential risk factors.

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.