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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.

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.

BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed. RESULTS: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17). CONCLUSIONS: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03937375 (Clinicaltrials.gov).

Aims: This prospective observational study evaluates the utility of non-invasive cardiac monitoring in obese patients in the day-surgery case, considering factors, such as Body Mass Index (BMI) and anaesthesia technique. Background: Obese patients are more likely to be admitted to hospital or to get hospitalized because they are more prone to concomitant diseases and obesity itself is not a contraindication to day surgery. Obese patients are a high-risk patient population that may particularly benefit from monitoring perioperative haemodynamic variations. Methods: In this observational study, we compared haemodynamic variations between overweight or obese and normal weight patients undergoing day-case surgery. We adopted NICOM® as a non-invasive cardiac output monitoring. Objective: The aim of the current study was to investigate the haemodynamic impact of BMI and anaesthesia technique during day-case surgery procedures. The other goal was to evaluate the feasibility and applications of non-invasive cardiac output monitoring among the obese population in day-surgery. Results: 74 patients were included in the study. 34 were overweight or obese (weight 84 ± 10 kg, height 160 ± 10 cm, BMI ≈ 30 kg/m2), 40 were normal weight (weight 63 ± 15 kg, height 160 ± 10 cm, BMI ≈ 22 kg/m2). Compared to normal-weight patients, obese patients show an increase in blood pressure with a return to baseline values at the end of surgery (p < 0.05). The Cardiac Output (CO) shows a similar trend, whereas the heart rate is normal. A decrease in the Cardiac Index (CI) during the operation was noticed in both groups, the one in obese patients (p = 0.24) being greater. In the same way, the Stroke Volume Index (SVI) was lower in obese patients during surgery (p < 0.05). In spinal anaesthesia, the Total Peripheral Resistance Index (TPRI) was not statistically different between the groups of study. As for the TPRI in obese patients, we reported values similar to the ones in non-obese patients in spinal anaesthesia. In local anesthesia, TPRI was higher in obese patients than in non-obese. Conclusion: Cardiovascular alterations in relation to obesity include an increase in blood pressure, CO and SV. An inadequate monitoring of haemodynamic parameters is a risk factor for perioperative complications. NICOM® provides a continuous, non-invasive haemodynamic measurement.

Introduction Low back pain (LBP) is a common problem, and facet joint pain is responsible for 15–45% of cases. Treatment is multidisciplinary, and when conservative measures are not sufficient, radiofrequency (RF) is often used. It allows the interruption of nociceptive input, producing a heat lesion in a continuous or pulsed mode. Methods Medical records of 60 patients who underwent pulsed RF denervation were examined. The standard procedure provided follow-up of pain intensity. Numerical rating scale (NRS) and Douleur Neuropathique en 4 Questions (DN4) were recorded before treatment, and 15 and 40 days, and 6 months after treatment. Oswestry Disability Index (ODI) and patient satisfaction were also recorded. Successful treatment was defined as more than a 50% reduction in the NRS scores at 6 months compared with pretreatment scores. Results Scores on the NRS and DN4 were statistically different over time (p

Neuropathic pain is defined as a painful condition caused by neurological lesions or diseases. Sometimes, neurological disorders may also be associated with neuropathic pain, which can be challenging to manage. For example, multiple sclerosis (MS) may cause chronic centralized painful symptoms due to nerve damage. Other chronic neuropathic pain syndromes may occur in the form of post-stroke pain, spinal cord injury pain, and other central pain syndromes. Chronic neuropathic pain is associated with dysfunction, disability, depression, disturbed sleep, and reduced quality of life. Early diagnosis may help improve outcomes, and pain control can be an important factor in restoring function. There are more than 100 different types of peripheral neuropathy and those involving sensory neurons can provoke painful symptoms. Accurate diagnosis of peripheral neuropathy is essential for pain control. Further examples are represented by gluten neuropathy, which is an extraintestinal manifestation of gluten sensitivity and presents as a form of peripheral neuropathy; in these unusual cases, neuropathy may be managed with diet. Neuropathic pain has been linked to CoronaVirus Disease (COVID) infection both during acute infection and as a post-viral syndrome known as long COVID. In this last case, neuropathic pain relates to the host's response to the virus. However, neuropathic pain may occur after any critical illness and has been observed as part of a syndrome following intensive care unit hospitalization.

Awake Fibreoptic Intubation (AFOI) is, nowadays, the gold standard in predicted difficult airway management. Numerous practice guidelines have been developed to assist clinicians facing with a difficult airway. If conducted without sedation, it is common that this procedure may lead to high patient discomfort and severe hemodynamic responses. Sedation is frequently used to make the process more tolerable to patients even if it is not always easy to strike a balance between patient comfort, safety, co-operation, and good intubating conditions. In the last years, many drugs and drug combinations have been described. This minireview aims to discuss the evidence supporting the use of Dexmedetomidine (DEX) in the AFOI management.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Current therapeutic strategies are based on the use of Temozolomide (TMZ) and antihuman epidermal growth factor receptor (EGFR) drugs, such as Afatinib. However, clinically relevant drug-resistance events are still present and closely related to a proinflammatory cancer brain microenvironment. The primary aim of this study is the association of Boswellic acid (BA), a molecule derived from Boswellia Serrata, with TMZ and Afatinibin different human GBM cells. We performed cell viability studies evaluating its antioxidant and anti-inflammatory effects analyzing p65/NF-κB and Leukotriene B4 expression and production of interleukins and growth factors (IL-8, IL-6, vascular endothelial growth factor, CXCL-12, and MMP-9). Considering the cardiotoxicity of TMZ and anti-EGFR drugs, we evaluated the putative cardioprotective effects of BA in adult cardiomyocytes. BA significantly increased the anticancer activities of TMZ and Afatinib. These effects are related to its anti-inflammatory and antioxidant effects, based on the inhibition of growth factors and proinflammatory interleukins. Notably, BA exerts also cardioprotective effects in combination to both drugs. This study provides evidences of anti-inflammatory, cardioprotective, and chemo sensitizing effects of BA in glioblastoma cells giving a rationale for new translational studies based on the use of this natural molecule during conventional therapies. Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Current therapeutic strategies are based on the use of Temozolomide (TMZ) and antihuman epidermal growth factor receptor (EGFR) drugs, such as Afatinib. However, clinically relevant drug-resistance events are still present and closely related to a proinflammatory cancer brain microenvironment. The primary aim of this study is the association of Boswellic acid (BA), a molecule derived from Boswellia Serrata, with TMZ and Afatinibin different human GBM cells. We performed cell viability studies evaluating its antioxidant and anti-inflammatory effects analyzing p65/NF-B and Leukotriene B4 expression and production of interleukins and growth factors (IL-8, IL-6, vascular endothelial growth factor, CXCL-12, and MMP-9). Considering the cardiotoxicity of TMZ and anti-EGFR drugs, we evaluated the putative cardioprotective effects of BA in adult cardiomyocytes. BA significantly increased the anticancer activities of TMZ and Afatinib. These effects are related to its anti-inflammatory and antioxidant effects, based on the inhibition of growth factors and proinflammatory interleukins. Notably, BA exerts also cardioprotective effects in combination to both drugs. This study provides evidences of anti-inflammatory, cardioprotective, and chemo sensitizing effects of BA in glioblastoma cells giving a rationale for new translational studies based on the use of this natural molecule during conventional therapies.

To evaluate whether pre-emptive skin analgesia using a lidocaine patch 5% would improve the effects of systemic morphine analgesia for controlling acute post-thoracotomy pain. Background: To evaluate whether pre-emptive skin analgesia using a lidocaine patch 5% would improve the effects of systemic morphine analgesia for controlling acute post-thoracotomy pain. Methods: This was a double-blind, placebo controlled, prospective study. Patients were randomly assigned to receive lidocaine 5% patch (lidocaine group) or a placebo (placebo group) three days before thoracotomy. Postoperative analgesia was induced in all cases with intravenous morphine analgesia. The intergroup differences were assessed in order to evaluate whether the lidocaine patch 5% would have effects on pain intensity when at rest and after coughing (primary end-point) on morphine consumption, on the recovery of respiratory function, and on peripheral painful pathways measured with N2 and P2 laser-evoked potential (secondary end-points). Results: A total of 90 patients were randomized, of whom 45 were allocated to the lidocaine group and 45 to the placebo group. Lidocaine compared with the placebo group showed a significant reduction in pain intensity both at rest (P = 0.013) and after coughing (P = 0.015), and in total morphine consumption (P = 0.001); and also showed a better recovery of flow expiratory volume in one second (P = 0.025) and of forced vital capacity (P = 0.037). The placebo group compared with the lidocaine group presented a reduction in amplitude of N2 (P = 0.001) and P2 (P = 0.03), and an increase in the latency of N2 (P = 0.023) and P2 (P = 0.025) laser-evoked potential. Conclusions: The preventive skin analgesia with lidocaine patch 5% seems to be a valid adjunct to intravenous morphine analgesia for controlling post-thoracotomy pain. However, our initial results should be corroborated/confirmed by larger studies.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication due to treatment with many commonly used anti-cancer agents. CIPN is a mainly sensory neuropathy that can be characterized by the appearance of motor and autonomic alterations. Clinicians may offer duloxetine (DLX) for patients with cancer experiencing CIPN. Our aim was to assess the non-inferiority of the analgesic effect and safety of tapentadol (TP) alone compared to duloxetine plus tapentadol administered to patients with CIPN. Methods: A total of 114 patients were enrolled in the study and randomized to receive tapentadol in a dosage of 50 to 500 mg/day (n = 56) or tapentadol plus duloxetine in a dosage of 60 to 120 mg/day (n = 58) for a period of 4 weeks. We evaluated the analgesia efficacy, defined as a decrease in pain on the NRS between the first administration and 28 days later. Secondary endpoints included analgesia efficacy at 28 and 42 days, defined by a decrease in DN4 and LEPs, decrease in quality of life, and the incidence of any serious or non-serious adverse events after the first administration. Results: In this randomized, double-blind trial comparing TP and TP plus DLX for CIPN management, TP was feasible and non-inferior to the association with DLX as far as the reduction of pain after chemotherapy at 28 days is concerned. Scores on other rating scales evaluating the quality of life, anxiety and depression, and the characteristics of pain revealed similar improvements associated with tapentadol versus duloxetine at these time points. Conclusion: The use of TP is a safe and effective analgesic therapy in patients with CIPN. Positive effects of TP were noted on the patients’ quality-of-life assessments.

Background/Aim: Postdural puncture headache (PDPH) is one of the earliest recognized complications of regional anesthesia after inadvertent dural puncture. Epidural blood patch (EBP) is the "gold standard" for the treatment of PDPH. Several alternatives have been suggested as peripheral nerve blocks. The aim of this systematic review was to find out the potential efficacy and safety of peripheral nerve blocks for the treatment of PDPH. Materials and Methods: The main databases were systematically searched in September 2020 for studies examining regional anesthesia and PDPH. Results: Nineteen studies were identified, including a total of 221 patients. Sphenopalatine ganglion block, greater occipital nerve block, and lesser occipital nerve block were performed. All participants reported a numeric rating scale (NRS) = 4 after 48 h. No major adverse events were reported. Approximately, 17% of patients underwent a second or more peripheral nerve blocks. In 30 participants, EBP was required. Conclusion: To our knowledge, this is the first systematic review on the use of peripheral nerve blocks to treat PDPH. Peripheral nerve blocks can be considered as analgesic options in the management of PDPH.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is often complicated by severe acute respiratory syndrome. The new coronavirus outbreak started in China in December 2019 and rapidly spread around the world. The high diffusibility of the virus was the reason for the outbreak of the pandemic viral disease, reaching more than 100 million infected people globally by the first three months of 2021. In the various treatments used up to now, the use of antimicrobial drugs for the management, especially of bacterial co-infections, is very frequent in patients admitted to intensive care. In addition, critically ill patients with SARS-CoV-2 infection are subjected to prolonged mechanical ventilation and other therapeutic procedures often responsible for developing hospital co-infections due to multidrug-resistant bacteria. Co-infections contribute to the increase in the morbidity–mortality of viral respiratory infections. We performed this study to review the recent articles published on the antibiotic bacterial resistance and viruses to predict risk factors of coronavirus disease 2019 and to assess the multidrug resistance in patients hospitalized in the COVID-19 area.

Background Gram-negative bacteria are an uncommon etiology of spontaneous community-acquired adult meningitis and meningoencephalitis. Escherichia coli is a Gram-negative bacterium that is normally present in the intestinal microbial pool. Some Escherichia coli strains can cause diseases in humans and animals, with both intestinal and extraintestinal manifestations (extraintestinal pathogenic Escherichia coli) such as urinary tract infections, bacteremia with sepsis, and, more rarely, meningitis. Meningitis continues to be an important cause of mortality throughout the world, despite progress in antimicrobial chemotherapy and supportive therapy. The mortality rate fluctuates between 15% and 40%, and about 50% of the survivors report neurological sequelae. The majority of Escherichia coli meningitis cases develop as a result of hematogenous spread, with higher degrees of bacteremia also being related to worse prognosis. Cases presenting with impaired consciousness (that is, coma) are also reported to have poorer outcomes. Case presentation We describe the case of a 48-year-old caucasian woman with meningoencephalitis, with a marked alteration of consciousness on admission, and septic shock secondary to pyelonephritis caused by Escherichia coli, treated with targeted antimicrobial therapy and immunoglobulin-M-enriched immunoglobulin (Pentaglobin) preparation as adjuvant therapy. Conclusion Despite the dramatic presentation of the patient on admission, the conflicting data on the use of immunoglobulins in septic shock, and the lack of evidence regarding their use in adult Escherichia coli meningoencephalitis, we obtained a remarkable improvement of her clinical condition, accompanied by partial resolution of her neurological deficits.

Introduction: The global pandemic of novel coronavirus disease 2019 (COVID-19) began in Wuhan, China in December 2019 and spread worldwide. This retrospective study summarizes clinical experience and analgo-sedation treatment used for this novel epidemic in an Italian ICU between February to May 2020. Methods: This is a retrospective trial of 72 patients with laboratory-confirmed SARS-CoV-2 infection (COVID-19) admitted to ICU between February15, 2020 and May 15, 2020. Main Outcomes are demographic, clinical data (age, sex, medical comorbidities, respiratory supports, positive end-expiratory pressure values (PEEP), fraction of inspired oxygen (FiO2), arterial partial pressure of oxygen (PaO2), sedatives and analgesic drugs, their dosage and way of administration, medical treatments and patients mortality), ventilation strategies, sedation management in ICUs and patient mortality. Results: The mean age of the 72 patients included in the study was 69 years (SD ±12), 77% were male. All patients required respiratory support and sedation management according to different techniques of ventilation: 100% received deep sedation (RASS-4) before intubation and invasive mechanical ventilation and 19% received light sedation (RASS-1) and noninvasive ventilation). Conclusions: Of the 72 patients admitted in ICUs, 92% died. A total of 608 patients admitted to the AORN dei Colli “Naples” with confirmed COVID-19. In this restrospective study we have analyzed 72 (out of 608) patients that were admitted to intensive care due to worsening clinical conditions. All patients required tracheal intubation and mechanical ventilation with deep sedation (RASS-4), while only 19% (patients required light sedation so RASS-1) were subsequentely swiched to light sedation because of the need of compliance with non-invasive ventilation. Sedation was obtained with propofol, remifentanil, midazolam and dexmedetomidine, according to hospital guidelines. ©2021 The Author(s). Published by MRE Press.

(1) Background: Surgery is a frequent cause of persistent pain, defined chronic post-surgical pain (CPSP). The capsaicin 8% patch (Qutenza®) is approved for the treatment of postherpetic neuralgia (PHN) and for diabetic peripheral neuropathy (DPN) of the feet. We propose a review of the literature on use of the capsaicin 8% patch to treat neuropathic pain associated with surgery; (2) Methods: We identified the articles by searching electronic databases using a combination of such terms as “capsaicin 8% patch”, “Qutenza®”, and “chronic postsurgical pain”; (3) Results: We identified 14 selected studies reporting on a total of 632 CPSP cases treated with capsaicin 8% patch. Treatment with the capsaicin 8% patch significantly reduced the average pain intensity. Only 5 studies reported adverse events (AEs) after the patch application. The most common AEs were erythema, burning sensation and pain; (4) Conclusions: Our review indicate that capsaicin 8% patch treatment for CPSP is effective, safe and well tolerated, but randomized controlled trials on efficacy, safety and tolerability should be conducted.

Background: Postdural puncture headache (PDPH) is one of the earliest recognized complications of regional anesthesia. It is a common complication after inadvertent dural puncture. When conservative management is ineffective, the Epidural Blood Patch (EBP) is the “gold standard” for the treatment of PDPH. Due to the potential complications of EBP, several alternatives have been promoted as peripheral nerve blocks.A systematic review of the use of regional anesthesia for PDPH is needed to identify an alternative method of pain management.Objectives: To systematically review literature to establish the efficacy and applicability of regional anesthesia used in the treatment of PDPH in the hospital setting.Methods: Embase, MEDLINE, Google Scholar and Cochrane Central Trials Register were systematically searched in May 2020 for studies examining regional anesthesia for PDPH. 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 peripheral nerve blocks for PDPH were included for a total of 221 patients. Sphenopalatine ganglion block (SPGB), greater occipital nerve block (GONB) and lesser occipital nerve block (LONB) were performed. All participants reported NRS lower than 4 after peripheral nerve blocks at 1, 24 and 48 hours. Only patients who experienced PDPH after diagnostic lumbar puncture reported NRS ≥ 4 after 48 hours. No adverse event was reported after the execution of nerve blocks, except an occasionally discomfort related to the insertion of cotton-tip applicators intranasally for SPGB. 17% of patients underwent a second or more peripheral nerve block due to uncontrolled pain. In 30 participants, EBP was required; none of cases followed spinal anesthesia.Conclusion: Peripheral nerve blocks can be considered as analgesic options in the management of PDPH, as not all cases require EBP for successful treatment. Treatment of PDPH with peripheral nerve blocks seems to be a minimal invasive, easy and effective method, which can offer to patients when conservative management is ineffective.

BackgroundBreast 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.ObjectivesTo systematically review literature to establish the efficacy and the safety of locoregional anesthesia used in the treatment of pain after breast surgery.MethodsEmbase, 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.ResultsNineteen 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.ConclusionThe 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.

Dexmedetomidine is a highly selective alpha-2 adrenoreceptor agonist without any effect on the GABA receptor. Its sedative, anxiolytic, analgesic, and sympatholytic activities together with opioid-sparing effects make it suitable for short- and long-term sedation in the intensive care setting. We report our experience with dexmedetomidine use during transfemoral transcatheter aortic valve implantation (TAVI) procedure as an alternative to general anesthesia. This is a retrospective analysis of high-risk patients undergoing dexmedetomidine infusion for the transfemoral TAVI procedure between July 2017 and October 2019. The primary outcome parameters were hemodynamic: heart rate (HR), mean arterial pressure (MAP); respiratory oxygen saturation (SpO2), pH, partial pressure of arterial oxygen (PaO2), partial pressure of arterial carbon dioxide (PaCO2), and sedation level (Richmond Agitation-Sedation Scale, RASS). The frequency of conversion to general anesthesia and the need for sedative “rescue therapy” were secondary endpoints. We also reported the overall anesthetic management and the incidence of intra- and postoperative complications. Eighty-five patients were evaluated (age 81.58 ± 5.23 years, 36.5% men, 63.5% women). High comorbidity, according to the Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM). The patients’ hemodynamic functions were kept normal. Complications such as cardiac arrest occurred in four patients; orotracheal intubation and cardiopulmonary resuscitation were necessary. Atrioventricular block occurred in nine patients. Respiratory parameters were maintained stable. Complications such as apnea, hypoventilation, and hypoxemia did not occur. All patients had RASS scores above or equal to 0 and − 1. No patient required rescue midazolam or fentanyl. No conversion to general anesthesia in patients sedated with dexmedetomidine was observed in the absence of hemodynamic complications caused by the surgical technique. In this series, sedation with dexmedetomidine for TAVI procedures with femoral access was proven effective and safe. Dexmedetomidine may be a valid alternative to general anesthesia in high-risk older patients undergoing transfemoral TAVI.

To date, the use of multimodal techniques can allow substantial opioid-sparing and can reduce pain by using the local and systemic effects of different types of analgesics. Aims: This case report describes a modified ERAS protocol specific for cardiac surgery with the ultrasound-guided block of the deep plane of the serratus muscle (SAP deep block) in a multimodal opioid-sparing approach. \ Two male patients, aged 62 and 67, undergoing elective mini-invasive off-pump Cardiopulmonary Bypass Grafting (CPB), were treated with an opioid-sparing multimodal anesthesiological approach based on the continuous ultrasound-guided SAP deep block. The continuous ultrasound-guided SAP deep block alone can be used in the case of mini-left thoracotomy off-pump cardiopulmonary bypass grafting implementing a multi-modal opioid-sparing strategy. It seems effective in obtaining good (2 hours) weaning from mechanical ventilation, quick (36 hours) discharge from post-operative intensive care, and good post-operative pain control (NRS < 5) even in elderly and frail patients.

Background Preoperative airway assessment plays a key role in the context of difficult airway management. Several scores have been proposed to predict difficult intubation including the el-Ganzouri index (EL.GA). Anatomical parameters such as the opening of the mouth or the circumference of the neck (which currently is not usually evaluated) are used to predict difficult intubation. The nutritional status of super-morbid obesity (body mass index [BMI] > 50 kg m-2) is a recognised risk factor for difficult intubation. Methods This is a single-centre, retrospective, observational study whose aim is to validate an additional parameter (anatomical plus nutritional) to the El.GA index, hence the choice of the acronym for the definition of the study: EL.GA+, in predictivity of airway management; multiple logistic regression analysis was performed to determine the predictive role of BMI, neck circumference and opening of the mouth of intubation difficulty measured with the gold standard. Results In total, 240 patients who had an elective surgical procedure under general anaesthesia, requiring endotracheal intubation, were examined. The predictive value of the EL.GA score was confirmed by the values of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) according to the data reported in the literature. Furthermore, based on the values of the PPV and NPV (0.69 and 0.60 respectively), neck circumference of 42.5 cm can be taken as a cut-off value for which EL.GA+ becomes predictive of difficult intubation in patients with mild obesity (BMI of 30 to 35). Conclusions The EL.GA+ score greatly increases the prediction of difficult laryngoscopy in mildly obese patients.

The purpose of this review is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care (benzodiazepines) compared to either the standard of care or other adjunctive treatment approaches (e.g. benzodiazepines plus propofol) for the treatment of alcohol withdrawal syndrome (AWS).Benzodiazepines have been the cornerstone of AWS therapy, but in some patients, AWS is refractory to high doses. Moreover, benzodiazepine use is burdened by excessive sedation, confusion and respiratory depression. Options for management of refractory AWS include the addition of phenobarbital, propofol and, more recently, dexmedetomidine to benzodiazepines therapy. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the intensive care unit.This review will consider studies including patients who are 18 years or older and are diagnosed with AWS. The exclusion criteria are a history of psychoactive substances or withdrawal states and/or severe neurologic disorder (e.g. traumatic brain injury, acute stroke, severe dementia, seizure disorder).This review will include only studies published in English, with no restrictions on the year of publication. Both randomized controlled trials and observational studies (including cohort and case-control studies) assessing the drug effectiveness and safety will be included. The databases utilized will include: PubMed, Embase and Cochrane Central Register of Controlled Trials. In addition, the trial registers to be searched will include: World Health Organization International Clinical Trials Registry Platform (ICTRP), U.S. National Library of Medicine Drug Information Portal and ClinicalTrials.gov.PROSPERO CRD42018084370.

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 17β-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 17β-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 17β-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 17β-estradiol at the dose of 100 nM is able to induce the release of CGRP from F11 cells; whereas, a higher dose of 17β-estradiol (200 nM) did not produce significant effects when compared to control. In conclusion, all these findings suggest that the 17β-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 aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS-314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti-inflammatory effects. Combination of Quercetin and SNS-314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS-314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti-tumor activity of these molecules. J. Cell. Physiol. 231: 1784-1795, 2016. © 2015 Wiley Periodicals, Inc.

Objectives We aimed at evaluating the effect of an antimicrobial stewardship (AMS) programme in two ICUs of a teaching hospital. Methods Between January 2017 and June 2018 we conducted a prospective, interventional, interrupted time series study, based on Prospective Audit and Feedback in two ICUs of an acute-care teaching hospital. The primary outcomes were the difference in the antibiotic consumption, and the incidence of bloodstream infections (BSI) caused by multidrug-resistant (MDR) organisms. The secondary outcomes included the hospital mortality rate, the mean length of stay and the antibiotic expense. Results During the study, 231 audits were performed, evaluating 693 antibiotic prescriptions. The programme led to a global reduction in antibiotic consumption, with a change in level (CL) of -324.8 DDD/100 patients-day (PD), p=0.04, and particularly in the use of fluoroquinolone: (CL: -63.48 DDD/100 PD, p

Background: Head and neck cancer affects approximately 382,000 new patients per year worldwide with a significant portion undergoing surgical treatment. During postoperative period key elements in the Intensive Care Unit (ICU) are airway management and pain control. Objective: We evaluated the average change of inpatient pain control using a Numerical Rating Score (NRS). We also evaluated the time of extubation after ICU admission recording the incidence of desaturation and the necessity of re-intubation. Secondary outcomes were the incidence of postoperative complications, included those narcotics-related, and the use of rescue analgesics. Methods: In this retrospective observational study, we analyzed data of registry before and after we have changed our postoperative analgesic protocol from remifentanil infusion to ketamine infusion. Results: Medical records of 20 patients were examined. 10 patients received 0.5 mg/kg ketamine bolus at the end of surgery, followed by a continuous infusion of 0.25 mg/kg/h. All patients presented a significant decrease in pain intensity from the 4th to 48th postoperative hour (p < 0.05), but statically not a significant difference in NRS score was recorded between the two groups. Time to extubation was shorter in ketamine group compared to the remifentanil group (112.30 min ± 16.78 vs. 78 min ± 14.17; p < 0.05). Desaturation rate was 10% in the remifentanil group, while no case was recorded in the ketamine group. Conclusion: The level of analgesia provided by ketamine and remifentanil was comparable. Ketamine was superior in ventilatory management of the patient with more rapid extubation and with no case of desaturation.

OBJECTIVES: To evaluate if the pre-emptive administration of ketamine would potentiate the effect of intravenous morphine analgesia in the management of post-thoracotomy pain. METHODS: This was a unicentre, double-blind, placebo-controlled, parallel-group, prospective study. Patients were randomly assigned to receive 1 mg/kg ketamine (ketamine group) or an equivalent dose of normal saline (placebo group) before thoracotomy in 1:1 ratio. All patients received postoperatively intravenous morphine administration as additional analgesic regimen. Primary end-point was the pain relief measured with Visual Analogue Scale at rest. The secondary end-points were the reduction of inflammatory response expressed by plasma C-reactive protein levels, the morphine consumption and the rate of side effects. The measurements were carried out 6, 12, 24, 36 and 48 hours postoperatively. RESULTS: A total of 75 patients were randomized of whom 38 were allocated to ketamine group and 37 to placebo group. Baseline characteristics were comparable. Ketamine compared with placebo group showed a significant reduction of pain scores (P= 0.01), C-reactive protein (P< 0.001) and morphine consumption (P< 0.001). No acute psychological side effects related to the use of ketamine were registered. CONCLUSIONS: The administration of ketamine before surgery may be an effective adjunct to intravenous morphine analgesia in acute post-thoracotomy pain management. In ketamine group, satisfaction of pain relief was significantly higher with a significant reduction of inflammatory response and morphine consumption compared with placebo group. Our results, if confirmed by larger studies, may be of clinical relevance in situations where epidural analgesia or other analgesic procedures different from systemic opioid analgesia are unavailable or contraindicated.

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling adverse event of most of commonly used antineoplastic agents. Previous studies have focused on several chemotherapeutic agents and reported that CIPN incidence varies from 19% to >85%. The mechanisms underlying CIPN are currently unknown. However, different theories have been proposed including microtubules dysfunction, mitochondrial dysfunction and mitochondrial toxicity, Glial pathway, substance P pathway, adenosine receptor pathway. CIPN is not simply to treat, and most randomized controlled trials failed to identify an effective therapy. Recent evidence supports the efficacy of serotonin (5-HT) and norepinephrine (NE) dual reuptake inhibitors (SNRI) in the treatment of neuropathy-related pain. Based on current evidence, we can speculate that duloxetine and topical menthol would improve CIPN pain as symptomatic treatment while, based on preclinical data, pifithrin-μ could be considered in future for the prevention of CIPN.

Background Descending necrotizing mediastinitis is a common and progressive polymicrobial infection involving the neck and chest with a high death rate (10 to 40%). From a microbiological point of view, descending necrotizing mediastinitis is sustained by Gram-positive bacteria (43–62%), anaerobes (46–78%), and, rarely, Gram-negative bacteria. Data collected during the Antibiotic Resistance-Istituto Superiore di Sanità project confirmed that Italy is positioned among the countries with the highest levels of resistance in most pathogenic species under surveillance. In particular, 32.9% of Klebsiella pneumoniae isolates were resistant to carbapenem, 33.6% of Staphylococcus aureus to methicillin, and 28.7% and 43.9% of Escherichia coli isolates to third-generation cephalosporins and fluoroquinolones, respectively. Case presentation We describe the case of a 38-year-old white man with septic shock due to descending necrotizing mediastinitis sustained by multidrug-resistant Gram-negative and Gram-positive bacteria treated after surgery with an IgM-enriched immunoglobulin preparation and polymyxin B hemoperfusion therapy. Conclusion Despite the contrasting data on the use of immunoglobulins and polymyxin B hemoperfusion in septic shock and the lack of literature in cases of acute mediastinitis caused by both Gram-negative and Gram-positive multidrug-resistant bacteria, we obtained an improvement in clinical conditions and the survival of our patient, against all odds.

Introduction Spontaneous fungal peritonitis (SFP) is an infection of ascitic fluid occurring in cirrhotic patients. SFP prevalence varies from 0% to 41% of patients with spontaneous peritonitis (SP) and a positive ascitic fluid culture. Cirrhotic patients with SFP who fail to show improvement with empirical antibiotic therapy, before the identification of the fungal pathogen, have high mortality (89.5-100%). Although the weight of the disease is so dramatic, more recent guidelines on infections in cirrhosis do not consider SFP management. The aim of this meta-analysis was to investigate the association between hospitalization (at least 48-72 hours after admission) and risk of SFP. Evidence acquisition A literature search was performed on PubMed, Scopus and Web of Science to identify relevant studies published up to March 2, 2017. Only observational studies that specify the etiology of SP were included. Data were pooled using risk difference as a summary measure and corresponding 95% confidence interval (CI). Evidence synthesis Thirteen cohort studies were included in the meta-analysis (12 retrospective and one prospective). A pooled risk difference, using a random effects model, of nosocomial versus non-nosocomial SFP was 2.9% (95% CI, 0.4% to 5.3%, P=0.024) with a no significant heterogeneity among studies (P=0.090, I²=37%). Conclusions This meta-analysis suggests that hospitalization is related to a significant increase of SFP risk.