Assistant Professor University of Parma Italy Pain Therapy Service Azienda Ospedaliera Universitaria Parma Italy Scientific Responsible of SIMPAR Editor in Chief "Fighting Pain" Section Editor "Minerva Anestesiologica" Associate Editor "Pain Research and Management" Address: Department of Surgical Sciences Via Gramsci 43126 Parma Italy
Chronic low back pain (CLBP) is a chronic pain syndrome in the lower back region, lasting for at ... more 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.
During pregnancy most of women will experience some kind of pain, either as a result of a pre-exi... more During pregnancy most of women will experience some kind of pain, either as a result of a pre-existing condition (low back pain, headache, fibromyalgia, and rheumatoid arthritis) or as a direct consequence of pregnancy (weight gain, postural changes, pelvic floor dysfunction, hormonal factors). However, chronic pain management during pregnancy and lactation remains a challenge for clinicians and pregnant women are at risk of undertreatment for painful conditions, because of fear about use of drugs during pregnancy. Few analgesic drugs have been demonstrated to be absolutely contraindicated during pregnancy and breastfeeding, but studies in pregnant women are not available for most of pain medications. The aim of this paper is to review the safety profile in pregnancy or lactation of the commonly prescribed pain medications and non-pharmacological treatments. In addition to the conventional classifications from the Food and Drug Administration and the American Academy of Paediatrics, authors analyzed the currently available clinical data from literature.
O
pioid analgesics are important therapeutic options for chronic non-cancer pain (CNCP), recogniz... more O pioid analgesics are important therapeutic options for chronic non-cancer pain (CNCP), recognized as a major public health issue with high social and economic burden. The increasing therapeutic opioid use for CNCP, misuse and abuse of prescription opioids have become matters of severe concern in USA . The recent position paper of the American Academy of Neurology (AA N) about the use of opioids in USA expresses growing alarms about opioid misuse/abuse, and has alerted physicians worldwide to rethink about their prescription practice. Current US practice in opioid prescription has been associated with morbidity and mortality of epidemic proportions: over 100,000 people directly or indirectly died from prescribed opioids in USA in the last twenty years, reaching 16,651 deaths in 2010. The actually alarming data from US have initiated pain physicians and researchers to re-evaluate their prescribing policies and attitudes for long-term treatment of non-cancer patients with opioids. In this position paper it is explained that any change in clinical behavior should not be based on an uncritical generalization of the US data that do not reflect the European situation. The primary objective of pain physicians remains to adequately treat chronic pain. Opioids are and will continue to remain an essential part of the “armamentarium against pain”; physicians should use them in the best way, i.e. after thorough diagnosis, assessment of alternative therapeutic options in the context of a multimodal treatment concept, and with repeated careful re-evaluations of the proper indication by a close long-term follow-up of any chronic opioid patient.
Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and... more Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and a periodic assessment of the patient are crucial to prevent misuse. A multidisciplinary group suggests strategies for all stakeholders involved in the management of pain and suggests the importance of the doctor-patient relationship.
Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channel... more Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release.
BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative ... more 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 ropiva-caine 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 C max 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. (Anesth Analg 2015;121:348–56)
Study objective: The study objective is to identify differences in postoperative pain management
... more 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. MeasurementsThe measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the postoperative (up to 5 days) period, chronic pain incidence (1 and 3months), side effects, and complications. Main results: We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in groupKvs 32%in group T, P = .43); the proportion of patientswithNRS≥4was similar in both groups, and the time trajectorieswere not significantly different (P for interaction = .24). Side effectswere 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.
Purpose To investigate interindividual variability in response to pain treatment, we characterize... more Purpose To investigate interindividual variability in response to pain treatment, we characterized postoperative patients for morphine metabolism and for COMT, OPRM1 and UGT2B7 polymorphisms. Methods A total of 109 patients treated with morphine were genotyped by DNA sequencing for 12 DNA polymorphisms of the COMT, OPRM1 and UGT2B7 genes. The plasma concentration of morphine and of M3G/M6G metabolites were evaluated by means of reversed phase high-performance liquid chromatography coupled with mass spectrometry. Results An association between average morphine consumption during the first 24 postoperative hours by patient-controlled analgesia (PCA) and COMT haplotypes was found. Specifically, patients with the diplotype for average pain intensity (APS/APS) required the lowest morphine doses compared to the other subjects (p=0.011). The APS haplotype contains an adenine corresponding to methionine, instead of valine, at position 158 of the COMT protein. Met/Met homo-zygous patients consumed significantly lower morphine doses than other subjects (p = 0.014); accordingly, Val158Met genotyping alone might be used in the clinical setting to predict PCA morphine need. Considering both COMT Val158Met and OPRM1 A118G polymorphisms, carriers of both the Met/Met and AA genotypes required less morphine than other subjects, although the difference was not significant. The analysis of UGT2B7 revealed the occurrence of two common haplotypes (G_C_C_A_C and A_T_T_G_T) that did not prove to be related with plasma morphine and M3G/M6G concentration. Conclusions By considering COMT, OPRM1, and UGT2B7 genotypes, as well as pharmacokinetic results, only COMT polymorphisms appear to be predictive of morphine need in postoperative pain therapy.
Continuous peripheral nerve blockade is an effective and
safe technique for postoperative analges... more Continuous peripheral nerve blockade is an effective and safe technique for postoperative analgesia, even when administered at home. To optimize this technique, further studies are needed to help minimize the risk of side effects, improve techniques to locate the targeted nerve (stimulating catheters or ultrasound imaging) and choose less toxic drugs (levobupivacaine and ropivacaine) with more effective infusion regimens.
Background. The Neuropathic Pain Scale is the first specific tool to measure and analyse pain due... more Background. The Neuropathic Pain Scale is the first specific tool to measure and analyse pain due to a lesion in the nervous system; this kind of pain is usually difficult to describe for the patient because it is characterized by unusual qualities. Aim of this study is to evaluate a possible relation between pain descriptions and underlying pathogenetic mechanisms. Methods. The Italian version of the Neuro-pathic Pain Scale has been administered to 145 patients with neuropathic pain due to chronic radiculopathy, diabetic neuropathy, post-traumatic neuropathy, Complex Regional Pain Syndrome or postherpetic neuralgia. As it has been done in Galer's study, the pre-dictive validity and the items' correlation have been evaluated; moreover, the structure validity of the scale has been studied. Results. Pain values were high in all pain syndromes with the prevalence of certain items in particular pathologies. The correlation of some items with " deep pain " and others with " superficial pain " was also observed. Conclusions. The results have confirmed the statistical validity of the Italian version of the scale; they also pointed out the usefulness of
Aim. To explore success, the percentage of patients who received definitive implants compared to ... more Aim. To explore success, the percentage of patients who received definitive implants compared to all patients screened, and efficacy, the percentage of patients that had improved in at least 3 of the 5 parameters after 1 year. In addition , we determined if there was a statistically significant reduction in pain and functional limiting. Finally, we wanted to investigate if the different paresthesia coverage has a different outcome after 1 year of SCS treatment. Methods. We studied 170 patients with neuro-pathic pain syndrome, failed back surgery syndrome and vascular disease, who received spinal cord stimulation (SCS) in the last 4 years. We evaluated, at the beginning and after 1 year, the patients with a questionnaire that assessed pain, what kind of function, drug consumption , patient's satisfaction and the improvement in the quality of life. Results. This study showed a success of more than 50% and an efficacy of more than 69.9%, with no significant differences in 3 different chronic pain conditions. Pain and functional limiting presented a statistically significant reduction. Finally, we confirmed that there were no statistically significant differences between patients with different paresthesia coverage. Conclusion. This prospective study confirmed that SCS had good success and efficacy in the treatment of several types of chronic pain. Finally, our study showed the importance of obtaining paresthesia in the affected area but it is not essential to cover the entire painful area.
Although regional anaesthesia has become safer, there are an increasing number of articles regard... more Although regional anaesthesia has become safer, there are an increasing number of articles regarding complications of regional blocks. During the last few years, many authors have suggested the use of ultrasound to minimize the appearance of complications. This review was performed, through a Medline research, to evaluate articles concerning ultra-sound and locoregional anaesthesia published until April 2005. A total of 39 articles were reviewed. Technical proce-d u res, the use of ultrasound guidance in epidural anesthesia, the application of this technique for peripheral nerve blocks, and its indications in pregnancy and in pediatric patients were considered. In these articles, all of the authors focused on the advantages of ultrasound guidance. With the help of this technique, correct catheter placement as close to the target as possible was obtained; the spread of local anesthetic administered around the nerve and its roots can be visualized, reducing the doses needed; in addition, it is possible to avoid the most common complications, such as intravascular injection, dura mater puncture, hematoma formation, and nerve injury. Ultrasound guidance is useful in facilitating peripheral and neuroaxial blocks and offers direct visualization of the target, adjacent stru c t u res, and local anesthetic spread. The advantages also include a decreased rate of complications and faster onset of blocks. Fi n a l l y, ultra-sound measurements can even result in suggestions to modify established block technique.
Most patients with advanced or metastatic cancer experience pain and despite several guidelines, ... more Most patients with advanced or metastatic cancer experience pain and despite several guidelines, undertreatment is well documented. A multicenter, open-label, prospective, non-randomised study was launched in Italy in 2006 to evaluate the epidemiology, patterns and quality of pain care of cancer patients. To assess the adequacy of analgesic care, we used a standardised measure, the pain management index (PMI), that compares the most potent analgesic prescribed for a patient with the reported level of the worst pain of that patient together with a selected list of clinical indicators. A total of 110 centres recruited 1801 valid cases. 61% of cases were received a WHO-level III opioid; 25.3% were classified as potentially undertreated, with wide variation (9.8 – 55.3%) according to the variables describing patients, centres and pattern of care. After adjustment with a multivariable logistic regression model, type of recruiting centre, receiving adjuvant therapy or not and type of patient recruited (new or already on follow-up) had a significant association with undertreatment. Non-compliance with the predefined set of clinical indicators was generally high, ranging from 41 to 76%. Despite intrinsic limitations of the PMI that may be considered as an indicator of the poor quality of cancer pain care, results suggest that the recourse to WHO third-level drugs still seems delayed in a substantial percentage of patients. This delay is probably related to several factors affecting practice in participating centres and suggests that the quality of cancer pain management in Italy deserves specific attention and interventions aimed at improving patients' outcomes.
Chronic low back pain (CLBP) is a chronic pain syndrome in the lower back region, lasting for at ... more 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.
During pregnancy most of women will experience some kind of pain, either as a result of a pre-exi... more During pregnancy most of women will experience some kind of pain, either as a result of a pre-existing condition (low back pain, headache, fibromyalgia, and rheumatoid arthritis) or as a direct consequence of pregnancy (weight gain, postural changes, pelvic floor dysfunction, hormonal factors). However, chronic pain management during pregnancy and lactation remains a challenge for clinicians and pregnant women are at risk of undertreatment for painful conditions, because of fear about use of drugs during pregnancy. Few analgesic drugs have been demonstrated to be absolutely contraindicated during pregnancy and breastfeeding, but studies in pregnant women are not available for most of pain medications. The aim of this paper is to review the safety profile in pregnancy or lactation of the commonly prescribed pain medications and non-pharmacological treatments. In addition to the conventional classifications from the Food and Drug Administration and the American Academy of Paediatrics, authors analyzed the currently available clinical data from literature.
O
pioid analgesics are important therapeutic options for chronic non-cancer pain (CNCP), recogniz... more O pioid analgesics are important therapeutic options for chronic non-cancer pain (CNCP), recognized as a major public health issue with high social and economic burden. The increasing therapeutic opioid use for CNCP, misuse and abuse of prescription opioids have become matters of severe concern in USA . The recent position paper of the American Academy of Neurology (AA N) about the use of opioids in USA expresses growing alarms about opioid misuse/abuse, and has alerted physicians worldwide to rethink about their prescription practice. Current US practice in opioid prescription has been associated with morbidity and mortality of epidemic proportions: over 100,000 people directly or indirectly died from prescribed opioids in USA in the last twenty years, reaching 16,651 deaths in 2010. The actually alarming data from US have initiated pain physicians and researchers to re-evaluate their prescribing policies and attitudes for long-term treatment of non-cancer patients with opioids. In this position paper it is explained that any change in clinical behavior should not be based on an uncritical generalization of the US data that do not reflect the European situation. The primary objective of pain physicians remains to adequately treat chronic pain. Opioids are and will continue to remain an essential part of the “armamentarium against pain”; physicians should use them in the best way, i.e. after thorough diagnosis, assessment of alternative therapeutic options in the context of a multimodal treatment concept, and with repeated careful re-evaluations of the proper indication by a close long-term follow-up of any chronic opioid patient.
Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and... more Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and a periodic assessment of the patient are crucial to prevent misuse. A multidisciplinary group suggests strategies for all stakeholders involved in the management of pain and suggests the importance of the doctor-patient relationship.
Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channel... more Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release.
BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative ... more 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 ropiva-caine 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 C max 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. (Anesth Analg 2015;121:348–56)
Study objective: The study objective is to identify differences in postoperative pain management
... more 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. MeasurementsThe measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the postoperative (up to 5 days) period, chronic pain incidence (1 and 3months), side effects, and complications. Main results: We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in groupKvs 32%in group T, P = .43); the proportion of patientswithNRS≥4was similar in both groups, and the time trajectorieswere not significantly different (P for interaction = .24). Side effectswere 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.
Purpose To investigate interindividual variability in response to pain treatment, we characterize... more Purpose To investigate interindividual variability in response to pain treatment, we characterized postoperative patients for morphine metabolism and for COMT, OPRM1 and UGT2B7 polymorphisms. Methods A total of 109 patients treated with morphine were genotyped by DNA sequencing for 12 DNA polymorphisms of the COMT, OPRM1 and UGT2B7 genes. The plasma concentration of morphine and of M3G/M6G metabolites were evaluated by means of reversed phase high-performance liquid chromatography coupled with mass spectrometry. Results An association between average morphine consumption during the first 24 postoperative hours by patient-controlled analgesia (PCA) and COMT haplotypes was found. Specifically, patients with the diplotype for average pain intensity (APS/APS) required the lowest morphine doses compared to the other subjects (p=0.011). The APS haplotype contains an adenine corresponding to methionine, instead of valine, at position 158 of the COMT protein. Met/Met homo-zygous patients consumed significantly lower morphine doses than other subjects (p = 0.014); accordingly, Val158Met genotyping alone might be used in the clinical setting to predict PCA morphine need. Considering both COMT Val158Met and OPRM1 A118G polymorphisms, carriers of both the Met/Met and AA genotypes required less morphine than other subjects, although the difference was not significant. The analysis of UGT2B7 revealed the occurrence of two common haplotypes (G_C_C_A_C and A_T_T_G_T) that did not prove to be related with plasma morphine and M3G/M6G concentration. Conclusions By considering COMT, OPRM1, and UGT2B7 genotypes, as well as pharmacokinetic results, only COMT polymorphisms appear to be predictive of morphine need in postoperative pain therapy.
Continuous peripheral nerve blockade is an effective and
safe technique for postoperative analges... more Continuous peripheral nerve blockade is an effective and safe technique for postoperative analgesia, even when administered at home. To optimize this technique, further studies are needed to help minimize the risk of side effects, improve techniques to locate the targeted nerve (stimulating catheters or ultrasound imaging) and choose less toxic drugs (levobupivacaine and ropivacaine) with more effective infusion regimens.
Background. The Neuropathic Pain Scale is the first specific tool to measure and analyse pain due... more Background. The Neuropathic Pain Scale is the first specific tool to measure and analyse pain due to a lesion in the nervous system; this kind of pain is usually difficult to describe for the patient because it is characterized by unusual qualities. Aim of this study is to evaluate a possible relation between pain descriptions and underlying pathogenetic mechanisms. Methods. The Italian version of the Neuro-pathic Pain Scale has been administered to 145 patients with neuropathic pain due to chronic radiculopathy, diabetic neuropathy, post-traumatic neuropathy, Complex Regional Pain Syndrome or postherpetic neuralgia. As it has been done in Galer's study, the pre-dictive validity and the items' correlation have been evaluated; moreover, the structure validity of the scale has been studied. Results. Pain values were high in all pain syndromes with the prevalence of certain items in particular pathologies. The correlation of some items with " deep pain " and others with " superficial pain " was also observed. Conclusions. The results have confirmed the statistical validity of the Italian version of the scale; they also pointed out the usefulness of
Aim. To explore success, the percentage of patients who received definitive implants compared to ... more Aim. To explore success, the percentage of patients who received definitive implants compared to all patients screened, and efficacy, the percentage of patients that had improved in at least 3 of the 5 parameters after 1 year. In addition , we determined if there was a statistically significant reduction in pain and functional limiting. Finally, we wanted to investigate if the different paresthesia coverage has a different outcome after 1 year of SCS treatment. Methods. We studied 170 patients with neuro-pathic pain syndrome, failed back surgery syndrome and vascular disease, who received spinal cord stimulation (SCS) in the last 4 years. We evaluated, at the beginning and after 1 year, the patients with a questionnaire that assessed pain, what kind of function, drug consumption , patient's satisfaction and the improvement in the quality of life. Results. This study showed a success of more than 50% and an efficacy of more than 69.9%, with no significant differences in 3 different chronic pain conditions. Pain and functional limiting presented a statistically significant reduction. Finally, we confirmed that there were no statistically significant differences between patients with different paresthesia coverage. Conclusion. This prospective study confirmed that SCS had good success and efficacy in the treatment of several types of chronic pain. Finally, our study showed the importance of obtaining paresthesia in the affected area but it is not essential to cover the entire painful area.
Although regional anaesthesia has become safer, there are an increasing number of articles regard... more Although regional anaesthesia has become safer, there are an increasing number of articles regarding complications of regional blocks. During the last few years, many authors have suggested the use of ultrasound to minimize the appearance of complications. This review was performed, through a Medline research, to evaluate articles concerning ultra-sound and locoregional anaesthesia published until April 2005. A total of 39 articles were reviewed. Technical proce-d u res, the use of ultrasound guidance in epidural anesthesia, the application of this technique for peripheral nerve blocks, and its indications in pregnancy and in pediatric patients were considered. In these articles, all of the authors focused on the advantages of ultrasound guidance. With the help of this technique, correct catheter placement as close to the target as possible was obtained; the spread of local anesthetic administered around the nerve and its roots can be visualized, reducing the doses needed; in addition, it is possible to avoid the most common complications, such as intravascular injection, dura mater puncture, hematoma formation, and nerve injury. Ultrasound guidance is useful in facilitating peripheral and neuroaxial blocks and offers direct visualization of the target, adjacent stru c t u res, and local anesthetic spread. The advantages also include a decreased rate of complications and faster onset of blocks. Fi n a l l y, ultra-sound measurements can even result in suggestions to modify established block technique.
Most patients with advanced or metastatic cancer experience pain and despite several guidelines, ... more Most patients with advanced or metastatic cancer experience pain and despite several guidelines, undertreatment is well documented. A multicenter, open-label, prospective, non-randomised study was launched in Italy in 2006 to evaluate the epidemiology, patterns and quality of pain care of cancer patients. To assess the adequacy of analgesic care, we used a standardised measure, the pain management index (PMI), that compares the most potent analgesic prescribed for a patient with the reported level of the worst pain of that patient together with a selected list of clinical indicators. A total of 110 centres recruited 1801 valid cases. 61% of cases were received a WHO-level III opioid; 25.3% were classified as potentially undertreated, with wide variation (9.8 – 55.3%) according to the variables describing patients, centres and pattern of care. After adjustment with a multivariable logistic regression model, type of recruiting centre, receiving adjuvant therapy or not and type of patient recruited (new or already on follow-up) had a significant association with undertreatment. Non-compliance with the predefined set of clinical indicators was generally high, ranging from 41 to 76%. Despite intrinsic limitations of the PMI that may be considered as an indicator of the poor quality of cancer pain care, results suggest that the recourse to WHO third-level drugs still seems delayed in a substantial percentage of patients. This delay is probably related to several factors affecting practice in participating centres and suggests that the quality of cancer pain management in Italy deserves specific attention and interventions aimed at improving patients' outcomes.
Uploads
(low back pain, headache, fibromyalgia, and rheumatoid arthritis) or as a direct consequence of pregnancy (weight
gain, postural changes, pelvic floor dysfunction, hormonal factors). However, chronic pain management during
pregnancy and lactation remains a challenge for clinicians and pregnant women are at risk of undertreatment for
painful conditions, because of fear about use of drugs during pregnancy. Few analgesic drugs have been demonstrated
to be absolutely contraindicated during pregnancy and breastfeeding, but studies in pregnant women are not
available for most of pain medications. The aim of this paper is to review the safety profile in pregnancy or lactation
of the commonly prescribed pain medications and non-pharmacological treatments. In addition to the conventional
classifications from the Food and Drug Administration and the American Academy of Paediatrics, authors analyzed
the currently available clinical data from literature.
pioid analgesics are important therapeutic options for chronic non-cancer pain (CNCP), recognized as a major public health issue with high social and economic burden. The increasing therapeutic opioid use for CNCP, misuse and abuse of prescription opioids have become matters of severe concern in USA . The recent position paper of the American Academy of Neurology (AA N) about the use of opioids in USA expresses growing alarms about opioid misuse/abuse, and has alerted physicians worldwide to rethink about their prescription practice. Current US practice in opioid prescription has been associated with morbidity and mortality of epidemic proportions: over 100,000 people directly or indirectly died from prescribed opioids in USA in the last twenty years, reaching 16,651 deaths in 2010. The actually alarming data from US have initiated pain physicians and researchers to re-evaluate their prescribing policies and attitudes for long-term treatment of non-cancer patients with opioids. In this position paper it is explained that any change in clinical behavior should not be based on an uncritical generalization of the US data that do not reflect the European situation. The primary objective of pain physicians remains to adequately treat chronic pain. Opioids are and will continue to remain an essential part of the “armamentarium against pain”; physicians should use them in the best way, i.e. after thorough diagnosis, assessment of alternative therapeutic options in the context of a multimodal treatment concept, and with repeated careful re-evaluations of the proper indication by a close long-term follow-up of any chronic opioid patient.
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.
MeasurementsThe measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the
postoperative (up to 5 days) period, chronic pain incidence (1 and 3months), side effects, and complications.
Main results: We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in
groupKvs 32%in group T, P = .43); the proportion of patientswithNRS≥4was similar in both groups, and
the time trajectorieswere not significantly different (P for interaction = .24). Side effectswere 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.
safe technique for postoperative analgesia, even when
administered at home. To optimize this technique, further
studies are needed to help minimize the risk of side effects,
improve techniques to locate the targeted nerve
(stimulating catheters or ultrasound imaging) and choose
less toxic drugs (levobupivacaine and ropivacaine) with
more effective infusion regimens.
(low back pain, headache, fibromyalgia, and rheumatoid arthritis) or as a direct consequence of pregnancy (weight
gain, postural changes, pelvic floor dysfunction, hormonal factors). However, chronic pain management during
pregnancy and lactation remains a challenge for clinicians and pregnant women are at risk of undertreatment for
painful conditions, because of fear about use of drugs during pregnancy. Few analgesic drugs have been demonstrated
to be absolutely contraindicated during pregnancy and breastfeeding, but studies in pregnant women are not
available for most of pain medications. The aim of this paper is to review the safety profile in pregnancy or lactation
of the commonly prescribed pain medications and non-pharmacological treatments. In addition to the conventional
classifications from the Food and Drug Administration and the American Academy of Paediatrics, authors analyzed
the currently available clinical data from literature.
pioid analgesics are important therapeutic options for chronic non-cancer pain (CNCP), recognized as a major public health issue with high social and economic burden. The increasing therapeutic opioid use for CNCP, misuse and abuse of prescription opioids have become matters of severe concern in USA . The recent position paper of the American Academy of Neurology (AA N) about the use of opioids in USA expresses growing alarms about opioid misuse/abuse, and has alerted physicians worldwide to rethink about their prescription practice. Current US practice in opioid prescription has been associated with morbidity and mortality of epidemic proportions: over 100,000 people directly or indirectly died from prescribed opioids in USA in the last twenty years, reaching 16,651 deaths in 2010. The actually alarming data from US have initiated pain physicians and researchers to re-evaluate their prescribing policies and attitudes for long-term treatment of non-cancer patients with opioids. In this position paper it is explained that any change in clinical behavior should not be based on an uncritical generalization of the US data that do not reflect the European situation. The primary objective of pain physicians remains to adequately treat chronic pain. Opioids are and will continue to remain an essential part of the “armamentarium against pain”; physicians should use them in the best way, i.e. after thorough diagnosis, assessment of alternative therapeutic options in the context of a multimodal treatment concept, and with repeated careful re-evaluations of the proper indication by a close long-term follow-up of any chronic opioid patient.
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.
MeasurementsThe measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the
postoperative (up to 5 days) period, chronic pain incidence (1 and 3months), side effects, and complications.
Main results: We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in
groupKvs 32%in group T, P = .43); the proportion of patientswithNRS≥4was similar in both groups, and
the time trajectorieswere not significantly different (P for interaction = .24). Side effectswere 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.
safe technique for postoperative analgesia, even when
administered at home. To optimize this technique, further
studies are needed to help minimize the risk of side effects,
improve techniques to locate the targeted nerve
(stimulating catheters or ultrasound imaging) and choose
less toxic drugs (levobupivacaine and ropivacaine) with
more effective infusion regimens.