Regional anesthesia techniques and postoperative delirium: systematic review and meta-analysis.

INTRODUCTION: Postoperative delirium is a frequent occurrence in the elderly surgical population. As a comprehensive list of predictive factors remains unknown, an opioid-sparing approach incorporating regional anesthesia techniques has been suggested to decrease its incidence. Due to the lack of conclusive evidence on the topic, we conducted a systematic review and meta-analysis to investigate the potential impact of regional anesthesia and analgesia on postoperative delirium. EVIDENCE ACQUISITION: PubMed, Embase, and the Cochrane central register of Controlled trials (CENTRAL) databases were searched for randomized trials comparing regional anesthesia or analgesia to systemic treatments in patients having any type of surgery. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We pooled the results separately for each of these two applications by random effects modelling. Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the certainty of evidence and strength of conclusions. EVIDENCE SYNTHESIS: Eighteen trials (3361 subjects) were included. Using regional techniques for surgical anesthesia failed to reduce the risk of postoperative delirium, with a relative risk (RR) of 1.21 (95% CI: 0.79 to 1.85); P=0.3800. In contrast, regional analgesia reduced the relative risk of perioperative delirium by a RR of 0.53 (95% CI: 0.42 to 0.68; P<0.0001), when compared to systemic analgesia. Post-hoc subgroup analysis for hip fracture surgery yielded similar findings. CONCLUSIONS: These results show that postoperative delirium may be decreased when regional techniques are used in the postoperative period as an analgesic strategy. Intraoperative regional anesthesia alone may not decrease postoperative delirium since there are other factors that may influence this outcome.

An Exploratory Pilot Study of Changes in Global DNA Methylation in Patients Undergoing Major Breast Surgery Under Opioid-Based General Anesthesia.

This study aimed to investigate DNA methylation levels in patients undergoing major breast surgery under opioid-based general anesthesia. Blood samples were collected from eleven enrolled patients, before, during and after anesthesia. PBMC were isolated and global DNA methylation levels as well as DNA methyltransferase (DNMT) and cytokine gene expression were assessed. DNA methylation levels significantly declined by 26%, reversing the direction after the end of surgery. Likewise, DNMT1a mRNA expression was significantly reduced at all time points, with lowest level of -68%. DNMT3a and DNMT3b decreased by 65 and 71%, respectively. Inflammatory cytokines IL6 and TNFα mRNA levels showed a trend for increased expression at early time-points to end with a significant decrease at 48 h after surgery. This exploratory study revealed for the first time intraoperative global DNA hypomethylation in patients undergoing major breast surgery under general anesthesia with fentanyl. The alterations of global DNA methylation here observed seem to be in agreement with DNMTs gene expression changes. Furthermore, based on perioperative variations of IL6 and TNFα gene expression, we hypothesize that DNA hypomethylation may occur as a response to surgical stress rather than to opiate exposure.

Serum sodium alterations in SARS CoV-2 (COVID-19) infection: impact on patient outcome.

OBJECTIVE: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. DESIGN AND METHODS: In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. RESULTS: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. CONCLUSIONS: These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.

The opioid sparing effect of erector spinae plane block for various surgeries: a meta-analysis of randomized-controlled trials.

INTRODUCTION: The erector spinae plane block (ESPB) is a newer fascial plane block which has been broadly applied for postoperative analgesia after various surgeries, but the effectiveness in these populations is not well established. EVIDENCE ACQUISITION: A systematic database search was conducted in PubMed, PMC, Embase, and Scopus for randomized controlled trials (RCTs) comparing ESPB with control, placebo, or other blocks. The primary outcome was intravenous opioid consumption in milligram morphine equivalents 24 h after surgery. Standardized mean differences (SMDs) with 95% confidence intervals (CI) were calculated using a random-effects model. EVIDENCE SYNTHESIS: A total of 29 RCTs were included. An analysis was conducted by subgroups differentiated by surgery type, 'no block' vs. ESPB, and other blocks vs. ESPB. ESPB was effective in reducing opioid consumption against no block for breast surgery (SMD -1.13; 95% CI), thoracic surgery (SMD -3.00; 95% CI), and vertebral surgery (SMD -1.78; 95% CI). ESPB was effective against alternative blocks for breast surgery (vs. paravertebral, SMD -1.07; 95% CI) and abdominal surgery (SMD -1.77; 95% CI). ESPB showed moderate effect in thoracic surgery against paravertebral (SMD 0.58; 95% CI) and against no block in abdominal surgery (SMD 0.80; 95% CI). In only one case did ESPB perform worse than another block: vs. PECS block for breast surgery (SMD 1.66; 95% CI). CONCLUSIONS: ESPB may be a useful addition to the multimodal analgesic regimen for a variety of surgeries especially when the alternative is no block. Unanswered questions include determining of the mechanism of action, refining of the EPSB technique, and establishing recommended local anesthetic dose and volume.

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

Non-invasive haemodynamic monitoring with Clearsight in patients undergoing spinal anaesthesia for total hip replacement. A prospective observational cohort study.

BACKGROUND: Patients undergoing elective primary total hip replacement and spinal anesthesia may encounter significant hemodynamic instability Objective: The study is aimed at observing the haemodynamic modifications after spinal anaesthesia during total hip replacement in patients managed to "preload independence" with goal directed fluid therapy (GDFT) and monitored non-invasively with Clearsight. METHODS: Thirty patients, aged 50-80 years, with an American Society of Anaesthesiologists' (ASA) score II-III, undergoing elective primary total hip replacement and spinal anaesthesia were enrolled. Patients were monitored with the EV1000 platform and the Clearsight finger-cuff and managed with a goal directed fluid therapy. RESULTS: The 79% of the population showed preload independence at baseline. After spinal, the 93% did not show a significant mean arterial pressure reduction. In our population, 79% reported a decrease >10% of the stroke volume during surgery, while 66% in the Recovery Room. Patients showed an improvement in mean arterial pressure, systemic vascular resistances indexed (SVRI), stroke volume (SV) and stroke volume indexed (SVI) at spinal resolution compared to baseline. CONCLUSIONS: Our cohort population showed hemodynamic stability throughout the study period, with increased SV and decreased SVRI at spinal resolution compared to basal values. Further randomized prospective studies are advocated in the same setting.

An Explorative Study of CYP2D6's Polymorphism in a Sample of Chronic Pain Patients.

BACKGROUND: A proper antalgic treatment is based on the use of titrated drugs to provide adequate relief and a good tolerability profile. Therapies have a variable effectiveness among subjects depending on medical and genetic conditions. CYP2D6 variations determine a different clinical response to most analgesic drugs commonly used in daily clinical practice by influencing the drugs' pharmacokinetics. This study was a monocentric clinical trial exploring the CYP2D6 variants in 100 patients with a diagnosis of chronic pain. METHODS: DNA was extracted to evaluate the genotype and to classify patients as normal-fast (gNMs-F), normal-slow (gNMs-S), ultrarapid (gUMs), intermediate (gIMs), and poor metabolizers (gPMs) using the Activity Score (AS). Information on therapies and general side effects experienced by patients was collected. Nongenetic co-factors were evaluated to examine the discrepancy between metabolic profile predicted from genotype (gPh) and metabolic profile (phenocopying). RESULTS: The distribution of our data underlined the prevalence of the gNMs-F (67%), whereas gNMs-S were 24%, gIMs 6%, gPMs 3%, and no gUMs were found, resulting in 33% of patients with reduced metabolic activity. In the analyzed population sample, 86% and 56% of patients, respectively, took at least one or two drugs inhibiting in vitro activity of the CYP2D6 enzyme. CONCLUSIONS: Over one-third of the enrolled patients showed altered CYP2D6 enzymatic metabolic activity, with a risk of phenocopying potentially due to polypharmacology. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03411759.

Oral prolonged-release oxycodone/naloxone offers equivalent analgesia to intravenous morphine patient-controlled analgesia after total knee replacement. A randomized controlled trial.

BACKGROUND: The purpose of this study was to determine whether oral prolonged-release oxycodone-naloxone combination (OXN) could provide equivalent analgesia and a side-effect profile similar to intravenous morphine patient-controlled analgesia (IVPCA) for the control of pain in the immediate postoperative period after total knee replacement (TKR). METHODS: All patients received a sciatic nerve block with 0.3% ropivacaine 15 mL, femoral nerve block with 0.5% ropivacaine 20 mL, spinal anesthesia and postoperative continuous femoral nerve infusion (ropivacaine 0.2% 4 mL/h). After surgery, patients were randomly allocated to receive either 10 +10 +5 mg controlled release OXN oral administration 12 hourly or IVPCA with morphine (2 mg bolus, no basal infusion). The primary outcome was the average rest and dynamic pain for the first 48 h postoperatively. Secondary outcomes were: post operative nausea vomiting (PONV) and the total morphine consumption. RESULTS: OXN group experienced better pain control at rest during the first (0.89±1.54 vs. 1.27±1.82, P=0.0019) and second (1.03±1.69 vs. 1.65±2.05, P=0.0006) postoperative period. There was no statistically significant difference in pain score during movement between the two groups. The secondary outcome measures showed no significant differences in the total morphine consumption (12.04±1.1 vs. 11.46±3.7 mg, P=0.20) or PONV (0.6±0.8 vs. 0.8±1.0, P=0.40). CONCLUSIONS: This study show that in the immediate postoperative period after TKR, the patients receiving oral prolonged-release OXN experienced the same to better pain control than those receiving morphine IVPCA, with a similar degree of PONV.

Effects of anaesthesia and analgesia on long-term outcome after total knee replacement: A prospective, observational, multicentre study.

BACKGROUND: Perioperative regional anaesthesia may protect from persistent postsurgical pain (PPSP) and improve outcome after total knee arthroplasty (TKA). OBJECTIVES: Aim of this study was to evaluate the impact of regional anaesthesia on PPSP and long-term functional outcome after TKA. DESIGN: A web-based prospective observational registry. SETTING: Five Italian Private and University Hospitals from 2012 to 2015. PATIENTS: Undergoing primary unilateral TKA, aged more than 18 years, informed consent, American Society of Anesthesiologists (ASA) physical status classes 1 to 3, no previous knee surgery. INTERVENTION(S): Personal data (age, sex, BMI and ASA class), preoperative pain assessed by numerical rating scale (NRS) score, and risk factors for PPSP were registered preoperatively. Data on anaesthetic and analgesic techniques were collected. Postoperative pain (NRS), analgesic consumption, major complications and patient satisfaction were registered up to the time of discharge. PPSP was assessed by a blinded investigator during a phone call after 1, 3 and 6 months, together with patient satisfaction, quality of life (QOL) and walking ability. MAIN OUTCOME MEASURES: Experience of PPSP according to the type of peri-operative analgesia. RESULTS: Five hundred sixty-three patients completed the follow-up. At 6 months, 21.6% of patients experienced PPSP, whereas autonomy was improved only in 56.3%; QOL was worsened or unchanged in 30.7% of patients and improved in 69.3%. Patients receiving continuous regional anaesthesia (epidural or peripheral nerve block) showed a lower NRS through the whole peri-operative period up to 1 month compared with both single shot peripheral nerve block and those who did not receive any type of regional anaesthesia. No difference was found between these latter two groups. Differences in PPSP at 3 or 6 months were not significantly affected by the type of anaesthesia or postoperative analgesia. A higher NRS score at 1 month, younger age, history of anxiety or depression, pro-inflammatory status, higher BMI and a lower ASA physical status were associated with a higher incidence of PPSP and worsened QOL at 6 months. CONCLUSION: Continuous regional anaesthesia provides analgesic benefit for up to 1 month after surgery, but did not influence PPSP at 6 months. Better pain control at 1 month was associated with reduced PPSP. Patients with higher expectations from surgery, enhanced basal inflammation and a pessimistic outlook are more prone to develop PPSP. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02147730.

Prilocaine hydrochloride 2% hyperbaric solution for intrathecal injection: a clinical review.

Prilocaine is a local anesthetic characterized by intermediate potency and duration and fast onset of action. As hyperbaric formulation of 5% solution, it was introduced and has been successfully used for spinal anesthesia since 1960. A new formulation of 2% plain and hyperbaric solution is currently available in Europe. Because of its lower incidence of transient neurological symptoms, prilocaine is suggested as substitute to lidocaine and mepivacaine in spinal anesthesia for ambulatory surgery, as well as a suitable alternative to low doses of long-acting local anesthetics. The National Library of Medicine database, the Excerpta Medica database, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials database, were searched for the period 1970 to September 2016, with the aim to identify studies evaluating the intrathecal use of 2% prilocaine. A total of 13 randomized clinical trials (RCTs), 1 observational study, 2 dose finding, and 4 systematic reviews has been used for this review. The studies evaluated showed that 2% hyperbaric prilocaine due to a favorable anesthetic and safety profile is an alternative drug to lidocaine and mepivacaine for spinal anesthesia of intermediate or short duration. In comparison with plain solutions, hyperbaricity remarkably accelerates the onset and offset times of intrathecal 2% prilocaine. Literature suggests a dose ranging between 40 and 60 mg of prilocaine for lower extremities and lower abdominal procedures lasting up to 90 min, whereas a dose ranging from 10 to 30 mg is appropriate for perineal surgery. Readiness for discharge occurs in ~4 h from spinal administration.

Future Perspectives of ERAS: A Narrative Review on the New Applications of an Established Approach.

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

Use of direct oral anticoagulants with regional anesthesia in orthopedic patients.

The use of direct oral anticoagulants including apixaban, rivaroxaban, and dabigatran, which are approved for several therapeutic indications, can simplify perioperative and postoperative management of anticoagulation. Utilization of regional neuraxial anesthesia in patients receiving anticoagulants carries a relatively small risk of hematoma, the serious complications of which must be acknowledged. Given the extensive use of regional anesthesia in surgery and the increasing number of patients receiving direct oral anticoagulants, it is crucial to understand the current clinical data on the risk of hemorrhagic complications in this setting, particularly for anesthesiologists. We discuss current data, guideline recommendations, and best practice advice on effective management of the direct oral anticoagulants and regional anesthesia, including in specific clinical situations, such as patients undergoing major orthopedic surgery at high risk of a thromboembolic event, or patients with renal impairment at an increased risk of bleeding.

The use of vitamin B1 as a perineural adjuvant to middle interscalene block for postoperative analgesia after shoulder surgery.

BACKGROUND: Perineural administration of thiamine, via axonal flow, could strenghthen synthesis of ACh in the dorsal horn inhibitory interneurons, thus potentiating analgesia. The purpose of the present retrospective analysis is therefore to investigate whether adding perineurally 2 mg/Kg of thiamine to 0.75% levobupivacaine in patients undergoing middle interscalene block may prolong the duration of analgesia. METHOD: The hospital records of all ASA status 1-2 patients, undergoing a single-shot interscalene block for arthroscopic rotator cuff repair from January 2011 to May 2012 were retrospectively reviewed. All blocks were performed with 0.75% levobupivacaine or a solution of thiamine hydrochloride and 0.75% levobupivacaine. The local anesthetic solution, postoperative visual analogue score for pain at rest and rescue medication were registered. We calculated the time interval elapsing between block anesthetic mixture injection and the patient's first analgesic requirement, ie time to end of analgesia. Eventual postoperative side effects were also reported. RESULTS: 59 patients received 0.4 ml/Kg of 0.75% levobupivacaine (Group L) and 51 patients received a mixture of 2 mg/Kg of thiamine hydrocloride (maximum dose 200 mg) with 0.4 ml/Kg of 0.75% levobupivacaine (Group B1). Tea was 11.4 ± 3.0 hours in Group L versus 17.6 ± 3.0 hours in Group B1 (p < 0.001). The scores for pain in the two Groups at the time of the first analgesic rescue were comparable. CONCLUSION: The present retrospective analysis suggests that thiamine helps to prolong postoperative analgesia when added to the local anesthetic solution. Further prospective studies are necessary to confirm these preliminary results.Word count: 250.

Transversus Abdominis Plane Block for Postoperative Analgesia in Patients Undergoing Total Laparoscopic Hysterectomy: A Randomized, Controlled, Observer-Blinded Trial.

BACKGROUND: In this randomized, controlled, observer-blinded study, we evaluated analgesia provided by transversus abdominis plane (TAP) block after elective total laparoscopic hysterectomy in terms of reduced postoperative morphine consumption as the primary end point. METHODS: Fifty-two patients were randomly divided into 2 groups: patients in group T (TAP, n = 26) received an ultrasound-guided bilateral TAP block with 40 mL of 0.375% levobupivacaine and morphine patient-controlled analgesia, whereas patients in group C (control, n = 26) received morphine patient-controlled analgesia. Secondary outcomes included pain measurements (Numeric Rating Scale from 0 to 10) during the first 24 hours postoperatively, times to postanesthesia care unit discharge, times to surgical ward discharge, incidence of postoperative nausea and vomiting, functional capacity measurements in terms of 2-minute walking test, and first oral solid intake. RESULTS: Demographic and anthropometric variables were similar in the 2 groups. The total dose of morphine consumed by patients during postanesthesia care unit stay was 6 (0-8) mg in group T vs 8 (5.5-8.5) mg in group C (P = 0.154). Postoperative morphine consumption during the first 24 hours was 10.55 ± 10.24 mg in group C vs 10.73 ± 13.45 mg in group T (P = 0.950). The 95% confidence interval of the difference between means of 24-hour morphine consumption was -7.45 to +7.09. The 2 groups were comparable. There were no significant differences in secondary outcome variables between groups. CONCLUSIONS: TAP block did not reduce morphine consumption during the first postoperative 24 hours after elective total laparoscopic hysterectomy.

Activity-based costing analysis of the analgesic treatments used in postoperative pain management in Italy.

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.

Iontophoretic transdermal fentanyl for the management of acute perioperative pain in hospitalized patients.

INTRODUCTION: Intravenous (I.V.) morphine administered through a patient-controlled system currently represents the gold standard treatment for moderate to severe acute postoperative pain. To fix the limitations showed by the available I.V. patient-controlled analgesia (PCA) systems that may restrict its use in the clinical practice a needle-free, iontophoretic, fentanyl patient-controlled transdermal system has been developed and recently approved by the United States Food and Drug Administration (FDA) and by the European Medicines Agency (EMA). AREAS COVERED: This review aims at describing the technology, pharmacology and clinical efficacy of fentanyl iontophoretic transdermal system (ITS) in the treatment of acute pain. A literature search was conducted in the PUBMED database using the term 'fentanyl iontophoretic transdermal system' through September 2015 and results from the main clinical trials are discussed. EXPERT OPINION: In 2015, the appropriate treatment of acute pain after surgery is still a challenge and it represents a primary goal in the care of the surgical patient. When regional analgesia techniques are not applicable and systemic analgesia is required, patient controlled systems represent the standard of care for opioid administration. The fentanyl ITS presents several potential advantages compared to the currently used PCA devices. In particular, it does not require intravenous lines and eliminates the potential for drug administration errors, observed with manually programmed standard PCA devices. Nevertheless, further studies are needed to address eventual inter-individual variability especially for opioid tolerant patients.

Lidocaine versus ropivacaine for postoperative continuous paravertebral nerve blocks in patients undergoing laparoscopic bowel surgery: a randomized, controlled, double-blinded, pilot study.

BACKGROUND AND OBJECTIVES: Lidocaine could provide many advantages in continuous regional anesthesia techniques, including faster onset, greater titratability, and lower cost than long-acting local anesthetics. This prospective, randomized, double-blinded, pilot study is therefore intended to compare lidocaine to ropivacaine in bilateral continuous paravertebral blocks using a multimodal approach for postoperative pain management following laparoscopic bowel surgery. METHODS: Thirty-five ASA I-III consecutive patients undergoing elective laparoscopic bowel surgery and bilateral thoracic paravertebral continuous blocks were analyzed: bilateral thoracic paravertebral infusions of ropivacaine 0.2% (Group Ropi, n=18) or lidocaine 0.25% (Group Lido, n=17) were started at 7 mL/h in the postanesthesia care unit. For each patient, we collected numerical rating scores (NRS) for pain at rest and during movement at baseline, at postanesthesia care unit discharge, at 24 hours and 48 hours after the end of surgery, as well as hydromorphone patient-controlled analgesia requirements, local anesthetic consumption, side effects, postoperative complications, and functional outcomes. RESULTS: No effect of group distribution on NRS scores for pain at rest or at movement (P=0.823 and P=0.146), nor on hydromorphone (P=0.635) or local anesthetic consumption (P=0.063) was demonstrated at any analyzed time point. Hospital length of stay and spontaneous ambulation were comparable between groups (P=0.636 and P=0.148). In the context of a multimodal approach, the two drugs showed comparable safety profiles. DISCUSSION: Lidocaine 0.25% and ropivacaine 0.2% provided similar analgesic profiles after elective abdominal surgeries, without any difference in terms of functional outcomes. The easier titratability of lidocaine together with its lower cost induced our clinical practice to definitely switch from ropivacaine to lidocaine for postoperative bilateral paravertebral continuous infusions.

Developments in managing severe chronic pain: role of oxycodone-naloxone extended release.

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

Periprocedural management of rivaroxaban-treated patients.

INTRODUCTION: The increasing and widespread use of direct oral anticoagulants (DOACs) demands guidelines and experts' consensus for their rational and safe use, especially in certain situations for which there is no evidence-based consensus, such as the periprocedural setting. Rivaroxaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF) and for treatment and prevention of venous thromboembolism (VTE) in major orthopedic surgery. This article is addressed to all the clinicians involved in the periprocedural approach of patients treated with rivaroxaban, with the aim to give practical recommendations to improve patients' management during and after surgery. AREAS COVERED: This article is based on a consensus of specialists involved in anticoagulant treatment and in periprocedural setting, including experts in thrombosis, cardiologists, internists, clinical pathologists and anesthesiologists. The authors performed a review of the literature and expressed statements based on the results of the review as well as on personal experience. EXPERT OPINION: Rivaroxaban is a safe and effective drug that simplifies management of anticoagulation also in patients undergoing invasive procedures. However, periprocedural management could be challenging and physicians must carefully balance the risk of bleeding and the risk of thrombosis.