What is the role of locoregional anesthesia in breast surgery? A systematic literature review focused on pain intensity, opioid consumption, adverse events, and patient satisfaction.

BACKGROUND: Breast surgery in the United States is common. Pain affects up to 50% of women undergoing breast surgery and can interfere with postoperative outcomes. General anesthesia is the conventional, most frequently used anaesthetic technique. Various locoregional anesthetic techniques are also used for breast surgeries. A systematic review of the use of locoregional anesthesia for postoperative pain in breast surgery is needed to clarify its role in pain management. OBJECTIVES: To systematically review literature to establish the efficacy and the safety of locoregional anesthesia used in the treatment of pain after breast surgery. METHODS: Embase, MEDLINE, Google Scholar and Cochrane Central Trials Register were systematically searched in Mars 2020 for studies examining locoregional anesthesia for management of pain in adults after breast surgery. The methodological quality of the studies and their results were appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and specific measurement properties criteria, respectively. RESULTS: Nineteen studies evaluating locoregional anesthesia were included: 1058 patients underwent lumpectomy/mastectomy, 142 breast augmentation and 79 breast reduction. Locoregional anesthesia provides effective anesthesia and analgesia in the perioperative setting, however no statistically significant difference emerged if compared to other techniques. For mastectomy only, the use of locoregional techniques reduces pain in the first hour after the end of the surgery if compared to other procedures (p = 0.02). Other potentially beneficial effects of locoregional anesthesia include decreased need for opioids, decreased postoperative nausea and vomiting, fewer complications and increased patient satisfaction. All this improves postoperative recovery and shortens hospitalization stay. In none of these cases, locoregional anesthesia was statistically superior to other techniques. CONCLUSION: The results of our review showed no differences between locoregional anesthesia and other techniques in the management of breast surgery. Locoregional techniques are superior in reducing pain in the first hour after mastectomy.

Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer.

The horizontal transfer of mtDNA and its role in mediating resistance to therapy and an exit from dormancy have never been investigated. Here we identified the full mitochondrial genome in circulating extracellular vesicles (EVs) from patients with hormonal therapy-resistant (HTR) metastatic breast cancer. We generated xenograft models of HTR metastatic disease characterized by EVs in the peripheral circulation containing mtDNA. Moreover, these human HTR cells had acquired host-derived (murine) mtDNA promoting estrogen receptor-independent oxidative phosphorylation (OXPHOS). Functional studies identified cancer-associated fibroblast (CAF)-derived EVs (from patients and xenograft models) laden with whole genomic mtDNA as a mediator of this phenotype. Specifically, the treatment of hormone therapy (HT)-naive cells or HT-treated metabolically dormant populations with CAF-derived mtDNAhi EVs promoted an escape from metabolic quiescence and HTR disease both in vitro and in vivo. Moreover, this phenotype was associated with the acquisition of EV mtDNA, especially in cancer stem-like cells, expression of EV mtRNA, and restoration of OXPHOS. In summary, we have demonstrated that the horizontal transfer of mtDNA from EVs acts as an oncogenic signal promoting an exit from dormancy of therapy-induced cancer stem-like cells and leading to endocrine therapy resistance in OXPHOS-dependent breast cancer.

Nociceptor plasticity: A closer look.

Nociceptors are receptors specifically involved in detecting a tissue damage and transducing it in an electrical signal. Nociceptor activation provoked by any kind of acute lesion is related to the release of several mediators of inflammation, within the framework of a process defined as "peripheral sensitization." This results in an exaggerated response to the painful stimulus, clinically defined as "primary hyperalgesia." The concept of "neuroplasticity" may explain the adaptive mechanisms carried out by the Nervous System in relation to a "harmful" damage; also, neuroplasticity mechanisms are also fundamental for rehabilitative intervention protocols. Here we review several studies that addressed the role of different receptors and ionic channels discovered on nociceptor surface and their role in pain perception. The changes in expression, distribution, and functioning of receptors and ionic channels are thought to be a part of the neuroplasticity property, through which the Nervous System constantly adapts to external stimuli. Moreover, some of the reviewed mediators are also been associated to "central sensitization," a process that results in pain chronicization when the painful stimulation is particularly prolonged or intense, and lastly leads to the memorization of the uncomfortable painful perception.

CGRP and Visceral Pain: The Role of Sex Hormones in In Vitro Experiment.

A large number of studies have showed that women reported feeling pain more acutely than men. In support of this hypothesis, many research groups proved that in different animals model of pain the sex hormones regulate the somatic and visceral sensitivity to different noxious stimuli. Therefore, in this study, we went to evaluate if estrogen hormones by regulating the CGRP levels are implicated during the visceral pain transmission. Toward this aim, we have investigated the effect of 17ß-estradiol in regulating the synthesis and release of CGRP, as well as the expression levels of the opioid receptor of type K. In order to gain information about the potential effects of 17ß-estradiol on K-opioid receptor expression and activity, we have cultured F11 cells. Our results revealed that, when F11 cells were short-term exposed (30 min) to 17ß-estradiol, the expression of the opioid K receptor was not significantly modified. We carried out enzyme immunoassay analysis to evaluate the potential effects of short-term exposure to 17-estradiol (30 min) on the release of CGRP in F11 cells. The results obtained showed that 17ß-estradiol at the dose of 100 nM is able to induce the release of CGRP from F11 cells; whereas, a higher dose of 17ß-estradiol (200 nM) did not produce significant effects when compared to control. In conclusion, all these findings suggest that the 17ß-estradiol-regulated release of CGRP could at least in part provide a rational explanation for the difference of gender in the visceral pain sensitivity. J. Cell. Biochem. 118: 510-517, 2017. © 2016 Wiley Periodicals, Inc.

The beneficial use of ultramicronized palmitoylethanolamide as add-on therapy to Tapentadol in the treatment of low back pain: a pilot study comparing prospective and retrospective observational arms.

BACKGROUND: This pilot study was designed to compare the efficacy of ultramicronized palmitoylethanolamide (um-PEA) as add-on therapy to tapentadol (TP) with TP therapy only in patients suffering from chronic low back pain (LBP). METHODS: This pilot observational study consists in two arms: the prospective arm and the retrospective one. In the prospective arm patients consecutively selected received um-PEA as add-on therapy to TP for 6 months; in the retrospective arm patients were treated with TP only for 6 months. Pain intensity and neuropathic component were evaluated at baseline, during and after 6 months. The degree of disability and TP dosage assumption were evaluated at baseline and after 6 months. RESULTS: Statistical analysis performed with generalized linear mixed model on 55 patients (30 in the prospective group and 25 in the retrospective group) demonstrated that um-PEA as add-on treatment to TP in patients with chronic LBP, in comparison to TP alone, led to a significantly higher reduction in pain intensity, in the neuropathic component, the degree of disability and TP dosage assumption. No serious side effects were observed. CONCLUSION: Overall, the present findings suggest that um-PEA may be an innovative therapeutic intervention as add-on therapy to TP for the management of chronic LBP with a neuropathic component, as well as to improve patient quality of life. Additionally, this combination treatment allowed a reduction in TP dose over time and did not show any serious side effects.

Loss of miR-101 expression promotes Wnt/ß-catenin signalling pathway activation and malignancy in colon cancer cells.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in Western countries. Although the aberrant expression of several microRNAs (oncomiRs) is associated with CRC progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that miR-101 expression is differentially impaired in CRC specimens, depending on tumour grade. miR-101 re-expression suppresses cell growth in 3D, hypoxic survival and invasive potential in CRC cells showing low levels of miR-101. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between miR-101 expression and important CRC pro-malignant features, such as inflammation, activation of the Wnt/ß-catenin signalling pathway and epithelial-mesenchymal transition (EMT). We then propose that up-regulated miR-101 may function as a tumour suppressor in CRC and that its pharmacological restoration might hamper the aggressive behaviour of CRC in vivo. MiR-101 expression may also represent a cancer biomarker for CRC diagnosis and prognosis.

Imipenem/Cilastatin/Relebactam for Complicated Infections: A Real-World Evidence.

(1) Background: Infections caused by multidrug-resistant (MDR) bacteria represent one of the major global public health problems of the 21st century. Beta-lactam antibacterial agents are commonly used to treat infections due to Gram-negative pathogens. New ß-lactam/ß-lactamase inhibitor combinations are urgently needed. Combining relebactam (REL) with imipenem (IMI) and cilastatin (CS) can restore its activity against many imipenem-nonsusceptible Gram-negative pathogens. (2) Methods: we performed a systematic review of the studies reporting on the use of in vivo REAL/IPM/CS. (3) Results: A total of eight studies were included in this review. The primary diagnosis was as follows: complicated urinary tract infection (n = 234), complicated intra-abdominal infections (n = 220), hospital-acquired pneumonia (n = 276), and ventilator-associated pneumonia (n = 157). Patients with normal renal function received REL/IPM/CS (250 mg/500 mg/500 mg). The most frequently reported AEs occurring in patients treated with imipenem/cilastatin plus REL/IPM/CS were nausea (11.5%), diarrhea (9.8%), vomiting (9.8%), and infusion site disorders (4.0%). Treatment outcomes in these high-risk patients receiving REL/IPM/CS were generally favorable. A total of 70.6% of patients treated with REL/IPM/CS reported a favorable clinical response at follow-up. (4) Conclusions: this review indicates that REL/IPM/CS is active against important MDR Gram-negative organisms.

Efficacy and Adverse Effects of IV Morphine for Burn Pain Management in the Emergency Department: An Observational Study.

INTRODUCTION: The management of pain following a burn is extremely complex because of the multifactorial nature of burn pain (nociceptive and neuropathic). In the pre-hospital setting and emergency department (ED), the main goal of acute pain management is to reduce the patient's pain, allowing them to maintain function and to prevent the chronification of pain. Opioids are used as first-line treatment in management of burn pain. The aim of our study was to evaluate the efficacy and adverse effects of intravenous (IV) morphine for burn pain management in the ED and to evaluate pain management in the pre-hospital setting. METHODS: In this single-center observational study, patients presenting with second- and third-degree burns were enrolled in our ED. Numerical Rating Scale (NRS) and Burn Specific Pain Anxiety Scale (BSPAS) were performed at ED admission and after 1 h. Pain medications administered before arrival in the ED were reported by the rescue team. All patients received IV acetaminophen every 8 h and IV morphine according NRS. RESULTS: Thirty patients were included in this study. At the time of arrival to the ED, > 90% of the patients reported severe pain; 95.8% of them received IV morphine to achieve pain relief. After 1 h, > 65% of patients had NRS < 3. The total amount of IV morphine was 18.12 ± 4.26 mg in the first hour. No adverse events were recorded. The BSPAS on admission to the ED was 34.8 ± 5.6, indicating severe anxiety. After 1 h, BSPAS was 12.8 ± 4.8, indicating mild anxiety. CONCLUSION: IV morphine used for burn pain management in the emergency setting significantly improves patient outcomes in terms of pain. IV morphine also reduced anxiety scores at 1 h.

The management of pain following a burn is extremely complex because of the multifactorial nature of burn pain. The main goal of acute pain management is to reduce the patient's pain, allowing them to maintain function and to prevent the chronification of pain. Opioids are used as first-line treatment in management of burn pain. In this single-center observational study, patients presenting with severe burns were enrolled in our hospital. Pain intensity and anxiety level were evaluated at admission and after 1 h. We evaluated pain treatment using intravenous (IV) morphine. Thirty patients were included in this study. At the time of arrival in hospital, almost all patients reported severe pain and received IV morphine to achieve pain relief. After 1 h, > 65% of patients had no pain. No adverse events were recorded related to morphine administration. The anxiety level improved after pain treatment. Finally, IV morphine used for burn pain management in the emergency setting significantly improves patient outcomes in terms of pain and reduced agitation.

Amyotrophic Lateral Sclerosis and Pain: A Narrative Review from Pain Assessment to Therapy.

Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.

Bickerstaff encephalitis in childhood: a review of 74 cases in the literature from 1951 to today.

Bickerstaff brainstem encephalitis (BBE) is a rare autoimmune disease characterized by the subacute onset of bilateral external ophthalmoplegia, ataxia, and decreased level of consciousness. BBE is part of a group of rare autoimmune diseases in children that can affect the nervous system at any level. The onset of neurological deficits is often sudden and nonspecific. The diagnosis is based on clinical findings and abnormal findings on cerebrospinal fluid (CSF), electroencephalography (EEG), electromyography (EMG), and magnetic resonance imaging (MRI). BBE is associated with the presence of the antiganglioside antibody, anti-GQ1b and anti-GM1. Intravenous immunoglobulin (IVIg) and plasma exchange are often used as treatments for these patients. We conducted a review on clinical presentation, diagnosis, treatment and outcome of reported cases of BBE. 74 cases are reported in the literature from the first cases described in 1951 to today. The prevalence is unknown while the incidence is higher in males. In 50% of cases, BBE occurs following respiratory or gastrointestinal tract infections. The most frequent initial symptoms were consciousness disturbance, headache, vomiting, diplopia, gait disturbance, dysarthria and fever. During illness course, almost all the patients developed consciousness disturbance, external ophthalmoplegia, and ataxia. Lumbar puncture showed pleocytosis or cytoalbuminological dissociation. Abnormal EEG and MRI studies revealed abnormalities in most cases. Anti-GQ1b antibodies were detected in more than half of the patients; anti-GM1 antibodies were detected in almost 40% of patients. Treatment guidelines are missing. In our analysis, steroids and IVIg were administered alone or in combination; as last option, plasmapheresis was used. BBE has a good prognosis and recovery in childhood is faster than in adulthood; 70% of patients reported no sequelae in our analysis. Future studies need to investigate pathogenesis and possible triggers, and therapeutic possibilities.

Burden of severe infections due to carbapenem-resistant pathogens in intensive care unit.

Intensive care units (ICU) for various reasons, including the increasing age of admitted patients, comorbidities, and increasingly complex surgical procedures (e.g., transplants), have become "the epicenter" of nosocomial infections, these are characterized by the presence of multidrug-resistant organisms (MDROs) as the cause of infection. Therefore, the perfect match of fragile patients and MDROs, as the cause of infection, makes ICU mortality very high. Furthermore, carbapenems were considered for years as last-resort antibiotics for the treatment of infections caused by MDROs; unfortunately, nowadays carbapenem resistance, mainly among Gram-negative pathogens, is a matter of the highest concern for worldwide public health. This comprehensive review aims to outline the problem from the intensivist's perspective, focusing on the new definition and epidemiology of the most common carbapenem-resistant MDROs (Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales) to emphasize the importance of the problem that must be permeating clinicians dealing with these diseases.

Pulsed Radiofrequency and Platelet Rich Plasma in Degenerative Joint Arthritis: Two Case Reports and Literature Analyses.

(1) Background: Osteoarthritis (OA) is a debilitating joint disease. The are several therapies available for OA. According to current knowledge, the combination of Platelet-Rich Plasma (PRP) and Pulsed Radiofrequency (PRF) can be applied in the treatment of pain of nociceptive origin due to peripheral tissue damage. (2) Methods: We performed a narrative review identifying the articles by searching electronic databases. A retrospective analysis of patients with OA treated with PRF and PRP in "Vito Fazzi" Hospital (Lecce, Italy) was performed. (3) Results: A total of four publications on the use of PRP and PRF in degenerative joint arthritis were included in our review. In our experience, two patients with OA were treated with PRP and PRF after unsuccessful conservative treatment. Patient pain score, daily activity ability, active range of activity, and muscle strength improved after treatment. Patients reported a higher level of satisfaction. No major adverse events were reported. (4) Conclusions: The goal of the combined application of the two treatments is to make full use of the analgesic effect of PRF and the repairing effect of PRP. At present, the therapeutic potential of PRP and PRF in OA remains unmet.

Comparison of McGrath Videolaryngoscope versus Macintosh Laryngoscope in Tracheal Intubation: An Updated Systematic Review.

(1) Background: In the last few years, many randomized controlled trials (RCTs) have compared direct Macintosh laryngoscopy with McGrath videolaryngoscopy in order to assess the potential benefits of the latter; the results were sometimes controversial. (2) Methods: We conducted a comprehensive literature search to identify our articles according to inclusion and exclusion criteria: to be included, each study had to be a prospective randomized trial or comparison between the McGrath videolaryngoscope and the Macintosh laryngoscope in an adult population. We did not include manikin trials or studies involving double-lumen tubes. (3) Results: 10 studies met the inclusion criteria necessary. In total, 655 patients were intubated with the McGrath and 629 with the Macintosh. In total, 1268 of 1284 patients were successfully intubated, showing equivalent results for the two devices: 648 of 655 patients with the McGrath videolaryngoscope and 620 of 629 patients with the Macintosh laryngoscope. No differences were noted in terms of hemodynamic changes or the incidence of adverse events. (4) Conclusions: We can assert that the McGrath videolaryngoscope and Macintosh laryngoscope, even if with equivalent tracheal intubation results, supplement each other.

Plasma glutamine decreases immediately after surgery and is related to incisiveness.

Glutamine (gln) is the most abundant free amino acid in the blood. It is involved in important metabolic and biochemical processes, like cell proliferation and oxidative stress. Previous studies have demonstrated that gln concentration in human plasma decreases in several conditions such as sepsis, ischemia-reperfusion, trauma, major surgery and burn. The aim of the present work was to compare the acute effects of different types of surgical interventions and of anesthetization on blood gln concentration. Plasma samples from 88 subjects (30 males and 58 females) were collected before and after major or minor surgery and the gln concentration was analyzed with high-performance liquid chromatography. The results showed that plasma gln concentration after surgery was lower than pre-surgery values and that in major surgery the decrease of gln was higher than in minor surgery. No significant effect was shown for sex or type of anesthesia. These results demonstrate the importance of a gln supplementation before a surgical intervention and show that the amount of gln supplementation should also be adjusted based on the type of surgery.

Pain in Intensive Care: A Narrative Review.

All critically ill adult patients in intensive care units (ICU) typically experience pain. Critically ill adults suffer pain of different intensities. It depends on individual characteristics, specific procedural interventions, and underlying diseases. Inadequate management of acute pain is a risk factor for the emergence of chronic pain, where the incidence is up to 33% into the ICU survivor population. For the management of pain, agitation, and delirium, several coexisting clinical practice guidelines have been published. The first problem is that the patient recovered in intensive care unit should not be able to communicate its pain state. Opioids are the analgesic drugs of choice in critically ill patients with non-neuropathic pain. All intravenous opioids have the same effects, respecting the equianalgesic table. Observational research has shown that opioids are the main analgesic treatment in over 80% of mechanically ventilated patients. It is interesting that opioid consumption in an ICU and the memory of painful experience are linked to the development of post-traumatic stress disorder after ICU discharge. In order to reduce the side effects and maintain analgesia, it is useful to associate adjuvant medications with opioids. An opportunity to improve patients' experience in an ICU is to manage pain through multimodal approaches.

Multimodal analgesia in neurosurgery: a narrative review.

Pain following brain surgery can compromise the result of surgery. Several pharmacological interventions have been used to prevent postoperative pain in adults undergoing brain surgery. Pain following craniotomy is considered to be moderate to severe during the first two post-operative days. Opioids have been historically the mainstay and are the current prominent strategy for pain treatment. They produce analgesia but may alter respiratory, cardiovascular, gastrointestinal, and neuroendocrine functions. All these side effects may affect the normal postoperative course of craniotomy by affecting neurological function and increasing intracranial pressure. Therefore, their use in neurosurgery is limited, and opioids are used in case of strict necessity or as rescue medication. In addition to opioids, drugs with differing mechanisms of actions target pain pathways, resulting in additive and/or synergistic effects. Some of these agents include acetaminophen/non-steroidal anti-inflammatory drugs (NSAIDs), alpha-2 agonists, NMDA receptor antagonists, gabapentinoids, and local anesthesia techniques. Multimodal analgesia should be a balance between adequate analgesia and less drug-induced sedation, respiratory depression, hypercapnia, nausea, and vomiting, which may increase intracranial pressure. Non-opioid analgesics can be an useful pharmacological alternative in multimodal regimes to manage post-craniotomy pain. This narrative review aims to outline the current clinical evidence of multimodal analgesia for post craniotomy pain control.

Cefiderocol for Carbapenem-Resistant Bacteria: Handle with Care! A Review of the Real-World Evidence.

(1) Background: healthcare-associated infections are one of the most frequent adverse events in healthcare delivery worldwide. Several antibiotic resistance mechanisms have been developed, including those to carbapenemase. Cefiderocol (CFD) is a novel siderophore cephalosporin designed to treat carbapenem-resistant bacteria. (2) Methods: we performed a systematic review of all cases reported in the literature to outline the existing evidence. We evaluated real-world evidence studies of CFD in the treatment of carbapenem-resistant (CR) bacteria. (3) Results: a total of 19 publications treating cases of infection by CR bacteria were included. The three most frequent CR pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. A regimen of 2 g every 8 h was most frequently adopted for CFD with a mean treatment duration of 25.6 days. CFD was generally well tolerated, with fewer side effects. The success rate of CFD therapy was satisfactory and almost 70% of patients showed clinical recovery; of these, nearly half showed negative blood cultures and infection-free status. (4) Conclusions: This review indicates that CFD is active against important GN organisms including Enterobacteriaceae, P. aeruginosa, and A. baumannii. CFD seems to have a safe profile.

Mechanisms of Action of Carbapenem Resistance.

Carbapenem antibiotics are the most effective antimicrobials for the treatment of infections caused by the most resistant bacteria. They belong to the category of ß-lactams that include the penicillins, cephalosporins, monobactams and carbapenems. This class of antimicrobials has a broader spectrum of activity than most other beta-lactams antibiotics and are the most effective against Gram-positive and Gram-negative bacteria. All ß-lactams antibiotics have a similar molecular structure: the carbapenems together with the ß-lactams. This combination gives an extraordinary stability to the molecule against the enzymes inactivating the ß-lactams. They are safe to use and therefore widespread use in many countries has given rise to carbapenem resistance which is a major global public health problem. The carbapenem resistance in some species is intrinsic and consists of the capacity to resist the action of antibiotics with several mechanisms: for the absence of a specific target, or an intrinsic difference in the composition of cytoplasmatic membrane or the inability to cross the outer membrane. In addition to intrinsic resistance, bacteria can develop resistance to antibiotics with several mechanisms that can be gathered in three main groups. The first group includes antibiotics with poor penetration into the outer membrane of bacterium or antibiotic efflux. The second includes bacteria that modify the target of the antibiotics through genetic mutations or post-translational modification of the target. The third includes bacteria that act with enzyme-catalyzed modification and this is due to the production of beta-lactamases, that are able to inactivate carbapenems and so called carbapenemases. In this review, we focus on the mode of action of carbapenem and the mechanisms of carbapenem resistance.

Opioid sparing effect of intravenous dexmedetomidine in orthopaedic surgery: a retrospective analysis.

BACKGROUND: Dexmedetomidine is a highly selective alpha-2 receptor agonist without any effect on the GABA receptor. It provides an excellent sedative and analgesic profile with few side effects. We report our experience with dexmedetomidine use during orthopaedic surgery under locoregional anaesthesia to ensure adequate sedation and optimal postoperative pain control. METHODS: In this retrospective analysis, we included 128 patients who underwent orthopaedic surgery between January 2019 and December 2021. All patients received the same local anaesthetic dose of 20 ml of ropivacaine 0.375% + mepivacaine 0.5% for axillary and supraclavicular block and 35 ml of ropivacaine 0.375% + mepivacaine 0.5% for triple nerve block (femoral, obturator and sciatic nerve). The cohort was divided into two groups based on sedation drugs used during surgery (dexmedetomidine, or group D, vs midazolam, or group M). All patients received postoperative 24-h analgesia consisting of 60 mg of ketorolac, 200 mg of tramadol and 4 mg of ondansetron. The primary outcome measured how many patients in the two groups required an analgesic rescue dose of pethidine and the time to first pethidine administration. To reduce confounding, we included patients in two groups with non-statistically different demo-anamnestic parameters and who received the same dose of intraoperative local anaesthetic and postoperative analgesia. RESULTS: The number of patients in group D who did not require a rescue dose of analgesia was significantly greater than in group M (49 vs 11, p < 0.001). Time-to-first postoperative opioid administration did not show a fundamental difference between the two groups under examination (523.75 ± 131.55 min vs 564 ± 117.84 min). Total opioid consumption was higher in the M group than in the D group (3529.8 ± 30.36 µg vs 1864.8 ± 31.59 µg, p 0.075), with a mean opioid consumption significantly higher in the M group than in the D group (26.26 ± 42.8 µg vs 69.21 ± 46.1 µg, p < 0.001): D group received 62.06% less opioid than M group. CONCLUSIONS: The continuous infusion of dexmedetomidine during orthopaedic surgery performed under locoregional anaesthesia has been shown to increase the analgesic effect of local anaesthetics and reduce the consumption of major opioids in the postoperative period. Dexmedetomidine offers a unique ability to supply sedation and analgesia without respiratory depression, having a wide safety margin and an excellent sedative capacity. It does not increase the rate of postoperative complications.

Non invasive hemodynamic monitoring for fluids and blood resuscitation during placenta praevia accreta cesarean delivery: a retrospective observational study.

BACKGROUND: We carry out a retrospective observational analysis of clinical records of patients with major placenta praevia who underwent cesarean section surgery over a period of 20 months in our hospital. Out of a total of 40 patients, 20 were subjected to Goal-Directed Therapy (GDT) implemented with non-invasive hemodynamic monitoring using the EV1000 ClearSight system (Group I) and 20 to standard hemodynamic monitoring (Group II). Given the risk of conspicuous blood loss, this study evaluate the impact on maternal and fetal health of GDT relative to standard hemodynamic monitoring. RESULTS: Average total infusion of fluids was 1600 +/- 350 ml. Use of blood products occurred in 29 patients (72,5%), of which 11 had a hysterectomy and 8 were treated with Bakri Balloons. For 2 patients > 1000 mL of concentrated red blood cells were used. When stroke volume index SVI dropped below 35 mL/m2/beat, it responded well to the infusion of at least 2 crystalloid boluses (5 ml/kg) in 7 patients. Cardiac index (CI) increased in 8 patients in concomitance with a reduction in medium arterial pressure (MAP), but the use of ephedrine (10 mg iv) re-established acceptable baseline values. Group I means are higher than Group II means for MAP, lower for RBC usage, end-of-surgery maternal lactates and fetal pH, and for LOS. Statistical analysis determines that the null hypotheses of equalities between Groups I and II can be rejected for all measures apart from MAP at baseline and induction. Proportions of serious complications in Groups I and II are respectively 10% and 32% and Boschloo's test rejects the null of equality of proportions against the alternative hypothesis of lower proportion of occurrence in Group I than in Group II. CONCLUSIONS: Hypovolemia can lead to vasoconstriction and inadequate perfusion with decreased oxygen delivery to organs and peripheral tissues and ultimately cause organ dysfunction. Despite the small sample size due to the rarity of the pathology, our statistical analysis finds evidence in favor of more favorable clinical outcomes for patients who received GDT implemented with non-invasive hemodynamic monitoring infusion relative to patients who received standard hemodynamic monitoring.