Andrea Fanelli

Article: Authors’ reply to “Role of erector spinae plane block in breast surgeries” - Minerva Anestesiologica 2022 October;88(10):871-2 - Minerva Medica - Journals

Article: Regional anesthesia techniques and postoperative delirium: systematic review and meta-analysis - Minerva Anestesiologica 2022 June;88(6):499-507 - Minerva Medica - Journals

Understanding neuropathic pain presents several challenges, given the various mechanisms underlying its pathophysiological classification and the lack of suitable tools to assess its diagnosis. Furthermore, the response of this pathology to available drugs is still often unpredictable, leaving the treatment of neuropathic pain still questionable. In addition, the rise of personalized treatments further extends the ramified classification of neuropathic pain. While a few authors have focused on neuropathic pain clustering, by analyzing, for example, the presence of specific TRP channels, others have evaluated the presence of alterations in microRNAs to find tailored therapies. Thus, this review aims to synthesize the available evidence on the topic from a clinical perspective and provide a list of current demonstrations on the treatment of this disease.

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. 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. 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. 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.

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.

Introduction: Abuse-deterrent formulations have been developed to reduce inappropriate opioid use. The aim of this paper is to review existing literature about currently available morphine abuse deterrent formulations. Areas covered: The US FDA has currently attributed an ‘abuse deterrent formulation’ label to two different morphine compounds: an agonist/antagonist combination, and a morphine formulation with physical barrier. The combination of morphine sulfate and naltrexone showed bioequivalence with extended release morphine. Naltrexone was found in low levels or non-detectable in most of the patients. If the capsules are tampered, the orally available naltrexone would be released, causing a decreased euphoria expected by the use of morphine. The application of physical and chemical barriers to the active compound aims at preventing manipulation of the opioid tablet. This abuse deterrent formulation obtained with a physical barrier did not reduce drug liking compared to ER morphine. Expert Commentary: Available data from literature suggest that both formulations may offer an alternative with lower abuse potential in the treatment of chronic pain. Nevertheless, current evidence suggests that only a little percentage of abusers may stop abusing drugs as result of reformulation. More post-marketing studies are advocated to evaluate the real impact of abuse deterrent formulations.

Perioperative regional anaesthesia may protect from persistent postsurgical pain (PPSP) and improve outcome after total knee arthroplasty (TKA). Aim of this study was to evaluate the impact of regional anaesthesia on PPSP and long-term functional outcome after TKA. A web-based prospective observational registry. Five Italian Private and University Hospitals from 2012 to 2015. 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. 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. Experience of PPSP according to the type of peri-operative analgesia. 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. 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. Clinicaltrials.gov identifier: NCT02147730

Objective: There are contrasting positions concerning the benefit–risk ratio of acetaminophen use for osteoarthritis (OA)-related pain. To clarify the effectiveness of acetaminophen or acetaminophen–codeine combinations according to their regimen of use, we evaluated whether being a regular user (adherent) of these medications decreased the occurrence of rescue therapy with non-steroidal anti-inflammatory drugs (NSAIDs). Methods: Using the Health Search IMS Health Longitudinal Patient Database, we formed a cohort of patients aged ≥18 years and newly treated with acetaminophen or acetaminophen–codeine combinations for OA between 1 January 2001 and 31 December 2013. These patients were followed up for one year in which they were categorized as regular or irregular users of these medications according to a variable medication possession ratio (VMPR) ≥ 50% or lower. We operationally defined the rescue therapy as the use of any NSAIDs prescribed for OA-related pain. Results: Overall, 40,029 patients (69.5% females; mean age: 68 ± 13.57) treated with acetaminophen or acetaminophen–codeine combinations formed the cohort. After the first year of treatment, regular users showed a statistically significantly lower risk of being prescribed with rescue therapy with NSAIDs (OR = 0.89; 95% CI 0.84–0.96). Conclusion: These findings show that regular use of acetaminophen or acetaminophen–codeine combinations may reduce the need for NSAIDs to treat OA-related pain.

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.