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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 (2 )., Main Outcome Measure(s): Differences in sex of morphine consumption rhythms over the 24 hours of the day., Results: Morphine consumption showed a statistically significant daily periodicity (p < 0.001) in our study population. Consumption was higher around 2 AM (rate 0.4 mg/min·patient) and lower around 12 PM (rate 0.05 mg/min·patient). Global consumption was not associated with the pump start time, age, or sex. The daily periodicity of morphine consumption was different between males and females (p = 0.004), with males consuming more morphine during the night., Conclusions: Our analysis confirmed the presence of daily rhythm for morphine consumption in patients treated with IV-PCA morphine after major abdominal surgery. A difference in the daily periodicity was observed between sexes. No difference emerged in daily periodicity for the categories of age and BMI.

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., Competing Interests: The authors declare that they have no competing interests.

Unlabelled: 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., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this analysis is to evaluate the costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in nine different Italian hospitals, defined as the cumulative cost of drugs, consumable materials and time required for anesthesiologists, surgeons and nurses to administer each analgesic technique., Methods: Nine Italian hospitals have been involved in this study through the administration of a questionnaire aimed to acquire information about the Italian clinical practice in terms of analgesia. This study uses activity-based costing (ABC) analysis to identify, measure and give value to the resources required to provide the therapeutic treatment used in Italy to manage the postoperative pain patients face after surgery. A deterministic sensitivity analysis (DSA) has been performed to identify the cost determinants mainly affecting the final cost of each treatment analyzed. Costs have been reclassified according to three surgical macro-areas (abdominal, orthopedic and thoracic) with the aim to recognize the cost associated not only to the analgesic technique adopted but also to the type of surgery the patient faced before undergoing the analgesic pathway., Results: Fifteen different analgesic techniques have been identified for the treatment of moderate to severe pain in patients who underwent a major abdominal, orthopedic or thoracic surgery. The cheapest treatment actually employed is the oral administration "around the clock" (€ 8.23), whilst the most expensive is continuous peripheral nerve block (€ 223.46). The intravenous patient-controlled analgesia costs € 277.63. In terms of resources absorbed, the non-continuous administration via bolus is the gold standard in terms of cost-related to the drugs used (€ 1.28), and when administered pro re nata it also absorbs the lowest amount of consumables (€0.58€) compared to all other therapies requiring a delivery device. The oral analgesic administration pro re nata is associated to the lowest cost in terms of health professionals involved (€ 6.25), whilst intravenous PCA is the most expensive one (€ 245.66), requiring a massive monitoring on the part of physicians and nurses., Conclusions: The analysis successfully collected information about costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in all the nine different Italian hospitals. The interview showed high heterogeneity in the treatment of moderate to severe pain after major abdominal, orthopedic and thoracic surgeries among responding anesthesiologists, with 15 different analgesic modalities reported. The majority of the analgesic techniques considered in the analysis is not recommended by any guideline and their application in real life can be one of the reasons for the high incidence of uncontrolled pain, which is still reported in the postoperative period. Health care costs have become more and more important, although the choice of the best analgesic treatment should be a compromise between efficacy and economic considerations.

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: 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., Methods/design: 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., Discussion: 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., Trial Registration: The trial was registered on ClinicalTrials.gov ( NCT02002663 ) on 24 Oct. 2013.

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.

Background: This study aims at investigating the effect of a single pre-operative oral administration of morphine sulphate (Oramorph®) on pain after laparoscopic cholecystectomy (LC)., Methods: Forty-one ASA I-III patients, aged 18-65 years, undergoing LC were randomly, double-blindly allocated to treatment (N.=20, 30mg Oramorph®, group M) or placebo (N.=21, group P). General anesthesia was maintained with propofol and remifentanil. All patients received ketamine 0.2 mg/kg iv at induction, intraoperative ketorolac 30mg iv and tramadol postoperatively (iv PCA: bolus 50 mg, lock-out 30 min, max 100 mg/4 hours). Numerical rating scale for pain (NRS), White's fast track and PADSS scores, tramadol consumption and adverse events were recorded for the first 24h. All patients underwent State Trait Anxiety Inventory (STAI) and Mini Mental State Examination (MMSE)., Results: Anthropometric characteristics, MMSE, STAI, ASA status, NRS rest, White's and PADDS scores, PONV incidence were similar. Group M showed significantly lower NRS on movement during the first 3 hours after awakening. Cumulative tramadol consumption was lower in group M than in group P (185±142 mg versus 263±199 mg, P=0.199)., Conclusion: Within a multimodal approach, a single preoperative oral administration of 30 mg of morphine sulphate in patients undergoing LC did not improve pain at rest, but improved NRS on movement during the first 3 hours after awakening. Group P required a higher mean dose of tramadol compared to Group M, although not significantly. The safety profile of Oramorph® allowed fast extubation and awakening times as well as prompt home discharge within 6 hours from surgery.

Background: The aim of this study was to evaluate the efficacy of tramadol as an adjuvant to the local anaesthetic solution in patients undergoing shoulder arthroscopy for rotator cuff tear after middle interscalene block (MIB)., Methods: We enrolled 120 patients (ASA I-II), scheduled for arthroscopic surgery for rotator cuff tear. The patients were sedated with midazolam 0.02 mg/kg and haloperidol 2 mg i.v. before performing MIB. All subjects underwent a MIB with 0.4 mL/kg of 0.5% levobupivacaine. After computerized randomization, all patients were allocated in 1 of 3 groups, each including 40 subjects. Group Placebo (Group P) received 0.4 mL/kg of 0.5% levobupivacaine plus isotonic sodium chloride for MIB and isotonic sodium chloride i.m. Group "Perineural Tramadol" (Group TPN) received 0.4 ml/Kg of 0.5% levobupivacaine plus 1.5 mg/kg of tramadol perineurally and isotonic sodium chloride i.m. Group "Intramuscular Tramadol" (Group TIM) received 0.4 ml/Kg of 0.5% levobupivacaine plus isotonic sodium chloride perineurally and 1.5 mg/kg of tramadol i.m., Results: The MIB onset times were not statistically different in the three groups. The duration of analgesia was significantly longer in Groups TPN and TIM, where tramadol was administered, either i.m. or perineurally, compared with the placebo group. A significant statistical difference was found in the duration of analgesia between the group TPN and TIM., Conclusion: The addition of tramadol to the local anaesthetic solution administered for MIB provided a longer duration of analgesia compared with placebo and i.m tramadol administration in patients undergoing arthroscopic surgery for rotator cuff tear.

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.

Background: The complexity of pain from laparoscopic cholecystectomy and the need for treating incident pain provide rationale for multipharmacological analgesia. We investigated the preoperative administration of controlled-release (CR) oxycodone as transition opioid from remifentanil infusion for pain after laparoscopic cholecystectomy., Methods: Fifty consecutive patients undergoing laparoscopic cholecystectomy were randomly, double-blindly assigned to treatment group (n=25, CR oxycodone: 1 h before surgery and 12 h after the first administration) or to the control group (n=25, placebo: administered at the same intervals). General anaesthesia was maintained with propofol and remifentanil target-controlled infusions (TCIs). All patients received ketorolac 30 mg i.v. Tramadol i.v. was administered for patient-controlled analgesia (PCA) postoperatively. Numerical rating scale for pain at rest and at movement (NRSr and NRSi), tramadol consumption, times to readiness to surgery and awakening, times to modified Aldrete's and modified Post-Anesthetic Discharge Scoring System (PADSS)>9 and side effects were evaluated., Results: All NRSr and NRSi and tramadol consumption were significantly lower in the treatment group. The oxycodone group showed higher modified Aldrete's scores at each time and reached a PADSS>9 faster. Side effects and postoperative nausea and vomiting episodes were comparable., Conclusions: We demonstrated the success of a multipharmacological treatment including opioid premedication with CR oxycodone used as transition opioid for TCI remifentanil infusion; the treatment group showed lower pain scores and rescue analgesic consumption, shorter time to discharge from recovery room and from surgical ward, and the same incidence of side effects, comparably to controls.

Although a wealth of evidence exists on effective postoperative pain (POP) treatment, surgical patients still suffer from inadequate analgesic regimens, and outcomes have been shown to improve only within the context of tightly controlled, randomized trials. The pathophysiology of pain seems to suggest that analgesic regimens aimed at inhibition of neurotransmission and neuroplastic phenomena should be instituted immediately before the painful stimuli are applied. Several protocols have been proposed, but the final choice should be made according to patients' needs, surgical indications, and institutional resources. Optimal POP management may succeed in improving outcomes only when combined with hospital-wide protocols for early rehabilitation and recovery; in the absence of adequate monitoring, equipment, motivation and coordination, even state-of-the-art techniques may fail to show results in terms of returning to daily life. Analgesic efficacy should always be balanced against safety and the ability to monitor patients in order to reduce complications that may actually impair recovery. A ''context-sensitive'' approach to POP, therefore, is suggested. Context-sensitive analgesia should be instituted as early as deemed necessary to avoid persistent pain, and it should be continued, with different modalities, until full recovery from surgery. In this way, it should constitute a ''bridge'' therapy from surgery to full healing. The use of neuroprotective agents to reduce the risk of postoperative hyperalgesia and other sensory disturbances should be considered in the context of specific surgical interventions.

Background: The aim of this prospective, randomized, double-blind study was to compare the efficacy of parecoxibfor postoperative analgesia after endoscopic turbinate and sinus surgery, with the non-selective non-steroid anti-inflammatory drug (NSAID), ketorolac., Methods: A total of 50 patients with an ASA physical status I-II, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy after local infiltration with 1% mepivacaine, were randomly assigned to receive intravenous administration of either 40 mg parecoxib (N.=25) or 30 mg ketorolac (N.=25), 15 min before the discontinuation of anaesthesia and then every 8 h postoperatively. A blinded observer recorded the incidence and severity of pain upon admission to the postanesthesia care unit (PACU), as well as 10, 20, and 30 min after PACU admission. Thereafter, observations continued every 1 h for the first 6 h, and then 12 h and 24 h after surgery., Results: The area under the curve of the visual analogue scale (AUCVAS) calculated during the study period was 635 (26-1 413) in the Parecoxib group and 669 (28-1 901) in the Ketorolac group (P=0.54). Rescue morphine analgesia was required by 12 patients (48%) in the Parecoxib group and 11 patients (44%) in the Ketorolac group (P<0.05); while mean morphine consumption was 5 +/- 2.5 mg and 5 +/- 2.0 mg in Ketorolac and Parecoxib groups, respectively (P<0.05). No differences in the incidence of side effects were recorded between the two groups. Patient satisfaction was similarly high in both groups, and all patients were discharged uneventfully 24 h after surgery., Conclusion: In patients undergoing endoscopic nasal surgery and local infiltration with 1% mepivacaine, parecoxib administered before discontinuing general anesthesia is as effective in treating early postoperative pain as ketorolac.

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 (i.v.) administration of either 40 mg of parecoxib (n=25) or 2 g of proparacetamol (n=25) 15 min before discontinuation of total i.v. 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 (AUC(VAS)) calculated during the study period was 669 (28-1901) cm x min in the proparacetamol group and 635 (26-1413) cm x 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 >or= 0.05), while mean morphine consumption was 5-3.5mg and 5-2.0 mg in the proparacetamol groups and parecoxib, respectively (p >or= 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.

Background and Aim of the Work: To evaluate the efficacy in terms of pain relief and degree of motor impairment of a continuous epidural infusion of 0.125% levobupivacaine in patients undergoing total knee replacement surgery., Methods: 186 patients receiving effective epidural analgesia with 0.125% levobupivacaine during the first 24 hours after surgery were randomly allocated to receive postoperative analgesia for the following 48 hours consisting in either a continued epidural infusion of 0.125% levobupivacaine (Levobupivacaine group, n = 96), or IV PCA morphine only (Morphine PCA group, n = 90). An independent observer recorded the average amount of morphine required per hour following randomisation, pain intensity, degree of motor blockade and occurrence of side effects., Results: Median (range) hourly morphine consumption during the study period was 0.21 (0.00-4.65) mg/hr in the Levobupivacaine group and 0.43 (0.04-4.65) mg/hr in the Morphine PCA group (P = 0.005). The quality of pain relief was adequate (VAS < 30 mm) in both groups, but patients in the Levobupivacaine group showed lower VAS values during motion than patients in the Morphine PCA group (P = 0.001). No differences in the proportion of patients with clinically relevant motor block (Bromage's score > or = 1) were reported between the two groups., Conclusions: Continuing the epidural infusion of a concentration of levobupivacaine as low as 0.125% improves pain relief with a 50% reduction of hourly morphine consumption after total knee replacement even during the second and third postoperative days, and does not result in a gross impairment of motor function.

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.

Unlabelled: We prospectively tested the hypothesis that the use of a stimulating catheter improves the efficacy of continuous posterior popliteal sciatic nerve block in 100 randomized patients scheduled for elective orthopedic foot surgery. After eliciting a sciatic mediated muscular twitch at < or = 0.5 mA nerve stimulation output, the perineural catheter was advanced 2-4 cm beyond the tip of the introducer either blindly (Group C; n = 50) or stimulating via the catheter (Group S; n = 50). A bolus dose of 25 mL of 1.5% mepivacaine was followed by a postoperative patient-controlled infusion of 0.2% ropivacaine (basal infusion: 3 mL/h; incremental dose: 5 mL; lockout time: 30 min). Propacetamol 2 g IV was administered every 8 h, and opioid rescue analgesia was available if required. Catheter placement required 7 +/- 2 min in Group S and 5 +/- 2 min in Group C (P = 0.056). A significantly shorter onset time of both sensory and motor blocks was noted in Group S. No difference in quality of pain relief at rest and during motion was reported between the groups. Median (range) local anesthetic consumption during the first 48 h after surgery was 239 mL (175-519 mL) and 322 mL (184-508 mL) in Groups S and C, respectively (P = 0.002). Rescue opioid analgesia was required by 12 (25%) and 28 (58%) patients in Groups S and C, respectively (P = 0.002). We conclude that the use of a stimulating catheter results in shorter onset time of posterior popliteal sciatic nerve block, similar pain relief with reduced postoperative consumption of local anesthetic solution, and less rescue opioid consumption., Implications: This prospective, randomized, blind investigation demonstrated that the use of a stimulating catheter for continuous posterior popliteal sciatic nerve block resulted in shorter onset time of sensory and motor blocks and less local anesthetic consumption and need for rescue pain medication after elective orthopedic foot surgery compared with blind catheter advancement.

We evaluated the effects of adding clonidine for continuous peripheral nerve infusions. Sixty patients undergoing total knee arthroplasty under combined single-injection sciatic block and continuous femoral infusion were randomly allocated to three groups: block induction with 0.75% ropivacaine followed by 0.2% ropivacaine (group control; n = 20); block induction with 0.75% ropivacaine and 1 microg/kg clonidine followed by 0.2% ropivacaine (group cloni-bolus; n = 20), and block induction with 0.75% ropivacaine and 1 microg/kg clonidine followed by 0.2% ropivacaine with 1 microg/mL clonidine (group cloni-infusion; n = 20). After surgery, continuous femoral infusion was provided with a patient-controlled infusion pump (basal infusion rate, 6 mL/h; incremental dose, 2 mL; lockout time, 15 min). The median (range) onset time of surgical block was 15 min (5-30 min) in group control, 10 min (5-35 min) in group cloni-bolus, and 10 min (5-30 min) in group cloni-infusion (P = 0.07). No differences were reported among groups in the degree of pain measured with the visual analog scale. The total consumption of local anesthetic solution after a 24-h infusion was 170 mL (144-220 mL) in group control, 169 mL (144-260 mL) in group cloni-bolus, and 164 mL (144-248 mL) in group cloni-infusion (P = 0.51); after the second day of infusion, total consumption was 168 mL (144-200 mL) in group control, 156 mL (144-288 mL) in group cloni-bolus, and 150 mL (144-210 mL) in group cloni-infusion (P = 0.48). Hemodynamic profiles and sedation were similar in the three groups. Motor function impairment after 48 h of infusion was observed in 27% of cloni-infusion patients but in only 6% of both the control and cloni-bolus groups (P = 0.05). We conclude that adding clonidine 1 microg/mL to local anesthetic for continuous femoral nerve block does not improve the quality of pain relief but has the potential for delaying recovery of motor function.

Study Objective: To compare the onset time and duration of epidural anesthesia, and the quality of postoperative analgesia produced by levobupivacaine, racemic bupivacaine, and ropivacaine., Design: Prospective, randomized, double-blinded study., Setting: Inpatient anesthesia at a University Hospital., Patients: 45 ASA physical status I, II, and III patients, undergoing elective total hip replacement., Interventions: After standard intravenous midazolam premedication and infusion of 500 mL of Ringer's acetate solution, patients were randomly allocated to receive epidural block with 0.5% levobupivacaine (n = 15), 0.5% bupivacaine (n = 15), or 0.5% ropivacaine (n = 15). Postoperatively, after pinprick sensation recovered at T(t), a patient-controlled epidural infusion was provided with 0.125% levobupivacaine, 0.125% bupivacaine, or 0.2% ropivacaine, respectively (baseline infusion rate 5 mL/hr; incremental bolus 2 mL, lockout time: 20 min). Intravenous ketoprofen was also available for rescue analgesia if required., Measurements and Main Results: The onset time of sensory block was 31 +/- 16 minutes with levobupivacaine, 25 +/- 19 minutes with bupivacaine, and 30 +/- 24 minutes with ropivacaine (p = 0.98), after a median (range) volume of 15 (10-18) mL in Group Levobupivacaine, 14 (10-18) mL in Group Bupivacaine, and 15 (10-18) mL in Group Ropivacaine (p = 0.85). Six patients in the ropivacaine group (40%) showed an intraoperative Bromage score <2 as compared with only three patients of Group Levobupivacaine (20%) and no patient of Group Bupivacaine (p = 0.02). Recovery of pinprick sensation at T(t) occurred after 214 +/- 61 minutes with levobupivacaine, 213 +/- 53 minutes with bupivacaine, and 233 +/- 34 minutes with ropivacaine (p = 0.26). A similar degree of pain relief was observed in the three groups without differences in local anesthetic consumption and need for rescue analgesia. Motor blockade progressively resolved without differences among the three groups., Conclusions: Levobupivacaine 0.5% produces an epidural block of similar onset, quality, and duration as the one produced by the same volume of 0.5% bupivacaine, with a motor block deeper than that produced by 0.5% ropivacaine. When prolonging the block for the first 12 hours after surgery with a patient-controlled epidural infusion, 0.125% levobupivacaine provides adequate pain relief after major orthopedic surgery, with similar recovery of motor function as compared with 0.125% bupivacaine and 0.2% ropivacaine.

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

Unlabelled: To compare the posterior popliteal and subgluteal continuous sciatic nerve block for anesthesia and acute postoperative pain management after foot surgery, 60 ASA physical status I and II patients undergoing elective orthopedic foot surgery were randomly assigned to either a Subgluteal group (n = 30) or Popliteal group (n = 30). Before surgery and after performing a femoral nerve block with 15 mL of 2% mepivacaine, we performed the sciatic nerve block with 20 mL of 0.75% ropivacaine using either a subgluteal or posterior popliteal approach, and the placement of a catheter came afterward. In the recovery room, the catheter was connected to a patient-controlled analgesia pump to infuse 0.2% ropivacaine (basal infusion rate of 5 mL/h, incremental bolus of 10 mL, and a lockout time of 60 min). There were no technical problems in catheter placement. Intraoperative efficacy of nerve block was similar in the two groups. Postoperative catheter displacement and occlusion were recorded in four patients in the Popliteal group and two patients in the Subgluteal group (P = 0.67). Both approaches provided similar postoperative analgesia. We conclude that the subgluteal approach is as effective and safe as the previously described posterior popliteal approach for continuous sciatic block and can be considered a useful alternative to anesthesia and acute postoperative analgesia after foot procedures., Implications: Comparing two different approaches for continuous sciatic nerve block after orthopedic foot surgery, this prospective, randomized study demonstrated that the subgluteal approach is as effective and safe as the previously described posterior popliteal approach, and can be considered a useful alternative to anesthesia and acute postoperative analgesia after foot procedures.

Background: The aim of this prospective, randomized, double-blind study was to evaluate the effects of adding 1 microg/kg clonidine to 20 ml of ropivacaine 0.75% for axillary brachial plexus anesthesia., Methods: With Ethical Committee approval and written consent, 30 ASA physical status I-II in-patients, undergoing upper extremity orthopedic procedures were randomly allocated to receive axillary brachial plexus block with 20 ml of 0.75% ropivacaine alone (group ropivacaine, n = 15) or 0.75% ropivacaine + 1 microg/kg clonidine (group ropivacaine-clonidine, n = 15). Nerve blocks were placed using a nerve stimulator with the multiple injection technique (stimulation frequency was 2 Hz; stimulation intensity was decreased to < or = 0.5 mA after each muscular twitch; the anesthetic volume was equally divided among arm flexion, arm extension, wrist flexion, and thumb adduction). A blinded observer recorded the time required to achieve surgical block [loss of pinprick sensation in the innervation areas of the hand (C6-C8) with concomitant inability to move the wrist and hand] and first analgesic request., Results: No differences in demography, degree of sedation, peripheral oxygen saturation, and hemodynamic variables were observed between the two groups. Readiness for surgery required 15 min (5-36 min) with 0.75% ropivacaine and 20 min (5-30 min) with the ropivacaine-clonidine mixture. The degree of pain measured at first analgesic request, and consumption of postoperative analgesics were similar in the two groups; while first postoperative analgesic request occurred after 13.8 h (25th-75th percentiles: 9.1-13 h) in the ropivacaine group and 15.2 h (25th-75th percentiles: 10.7-16 h) in the ropivacaine-clonidine group (p = 0.04)., Conclusions: Adding 1 microg/kg clonidine to 20 ml of ropivacaine 0.75% for axillary brachial plexus anesthesia provided a 3 h delay in first analgesic request postoperatively, without clinically relevant effects on the degree of sedation and cardiovascular homeostasis.

Unlabelled: To evaluate the effects of adding small-dose clonidine to 0.75% ropivacaine during peripheral nerve blocks, 30 ASA physical status I and II patients undergoing hallux valgus repair under combined sciatic-femoral nerve block were randomly allocated in a double-blinded fashion to receive block placement with 30 mL of either 0.75% ropivacaine alone (group Ropivacaine, n = 15) or 0.75% ropivacaine plus 1 microg/kg clonidine (group Ropivacaine-Clonidine, n = 15). Hemodynamic variables, oxygen saturation, and levels of sedation, as well as the time required to achieve surgical block and time to first analgesic request, were recorded by a blinded observer. Time to surgical blockade required 10 min in both groups. Patients in the Ropivacaine-Clonidine group were more sedated than patients in the Ropivacaine group only 10 min after block placement. No differences in oxygen saturation and hemodynamic variables, degree of pain measured at first analgesic request, and consumption of postoperative analgesics were observed between the two groups. The mean time from block placement to first request for pain medication was shorter in group Ropivacaine (13.7 h; 25th-75th percentiles: 11. 8-14.5 h) than in group Ropivacaine-Clonidine (16.8 h; 25th-75th percentiles: 13.5-17.8 h) (P = 0.038). We conclude that adding 1 microg/kg clonidine to 0.75% ropivacaine provided a 3-h delay in first request for pain medication after hallux valgus repair, with no clinically relevant side effects., Implications: This prospective, randomized, double-blinded study demonstrated that, when providing combined sciatic-femoral nerve block for hallux valgus repair, the addition of 1 microg/kg clonidine to 0.75% ropivacaine prolongs the duration of postoperative analgesia by 3 h, with only a slight and short-lived increase in the degree of sedation and no hemodynamic adverse effects.

Purpose: To compare analgesic efficacy and occurrence of motor block and other side effects during patient supplemented epidural analgesia (PSEA) with either ropivacaine/fentanyl or bupivacaine/fentanyl mixtures., Methods: In a prospective, randomized, double-blind study, 32 ASAI-III patients undergoing major abdominal surgery received an epidural catheter at the T8- T10, followed by integrated general epidural anesthesia. Postoperative epidural analgesia was provided using a patient controlled pump with either ropivacaine 0.2%/2 microg x ml(-1) fentanyl (group Ropivacaine, n = 16) or bupivacaine 0.125%/2 microg x ml(-1) fentanyl (group Bupivacaine, n = 16) [background infusion 4-6 ml x hr(-1), 1.5 ml Incremental Doses and 20 min lock out]. Verbal pain rating score, number of incremental doses, consumption of epidural analgesic solution and rescue analgesics, sedation (four-point scale), and pulse oximetry were recorded by a blind observer for 48 hr after surgery., Results: No differences in pain relief, motor block, degree of sedation, pulse oximetry and other side effects were observed between the two groups. The number of incremental doses and the volume of analgesic solution infused epidurally were higher in patients receiving the bupivacaine/fentanyl mixture (10 [0-52] I.D. and 236 [204-340] ml) than in patients receiving the ropivacaine/fentanyl solution (5 [0-50] I.D. and 208 [148-260] ml) (P = 0.03 and P = 0.05, respectively)., Conclusion: Using a ropivacaine 0.2%/2 microg x ml(-1) fentanyl mixture for patient supplemented epidural analgesia after major abdominal surgery provided similar successful pain relief as bupivacaine 0.125%/2 microg x ml(-1) fentanyl, but patients receiving bupivacaine/fentanyl requested more supplemental.

Purpose: To compare epidural infusions of bupivacaine-fentanyl and bupivacaine-morphine mixtures for postoperative pain relief after total hip replacement., Methods: In a prospective, randomized, double-blind study, 30 ASA physical status I-II patients undergoing total hip replacement were studied. Anaesthesia was provided by combined general/epidural anaesthesia without epidural opioids. Postoperative epidural analgesia was by continuous infusion of bupivacaine 0.125% (4 ml.hr-1) with either 0.05 mg.ml-1 morphine (morphine, n = 15) or 0.005 mg.ml-1 fentanyl (fentanyl, n = 15). Visual analogue pain scale (VAS), sedation (four-point scale), respiratory rate, pulse oximetry, rescue analgesics and supplemental oxygen were recorded by a blind observer at 1, 3, 6, 9, 12 and 24 hr after surgery., Results: No differences in pain relief, sedation, or non-respiratory side effects were observed between the two groups. Rescue analgesics were required in three patients in the fentanyl group (20%) and in two receiving morphine (13.3%) (P:NS). Two patients in the fentanyl group and three in the morphine group required oxygen due to SpO2 < 90% (P:NS). Both opioid/bupivacaine mixtures decreased haemoglobin oxygen saturation compared with preoperative values. The mean +/- SD SpO2 values measured at 3, 6, 12 and 24 hr were 94.4 +/- 1, 92.6 +/- 0.9, 92 +/- 0.8, and 92.8 +/- 1 in the morphine group, 95.3 +/- 0.5, 95 +/- 0.5, 94.6 +/- 1.2, and 95.6 +/- 1 in the fentanyl group (P < 0.05)., Conclusion: Continuous epidural infusion of bupivacaine-morphine or bupivacaine-fentanyl mixtures provided similar pain relief. Patients receiving morphine showed a more marked decrease in SpO2 than those receiving fentanyl. However, the average SpO2 remained > 90% in both groups.