Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

Red Blood Cell Transfusion in the Intensive Care Unit.

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice. Objective: To evaluate and describe ICU RBC transfusion practices worldwide. Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks. Exposure: ICU stay. Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused. Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL. Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

CB2 Receptor as Emerging Anti-Inflammatory Target in Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is a very severe X-linked dystrophinopathy. It is due to a mutation in the DMD gene and causes muscular degeneration in conjunction with several secondary co-morbidities, such cardiomyopathy and respiratory failure. DMD is characterized by a chronic inflammatory state, and corticosteroids represent the main therapy for these patients. To contradict drug-related side effects, there is need for novel and more safe therapeutic strategies. Macrophages are immune cells stringently involved in both physiological and pathological inflammatory processes. They express the CB2 receptor, one of the main elements of the endocannabinoid system, and have been proposed as an anti-inflammatory target in several inflammatory and immune diseases. We observed a lower expression of the CB2 receptor in DMD-associated macrophages, hypothesizing its involvement in the pathogenesis of this pathology. Therefore, we analyzed the effect of JWH-133, a CB2 receptor selective agonist, on DMD-associated primary macrophages. Our study describes the beneficial effect of JWH-133 in counteracting inflammation by inhibiting pro-inflammatory cytokines release and by directing macrophages' phenotype toward the M2 anti-inflammatory one.

Clinical, Genetic, and Histological Characterization of Patients with Rare Neuromuscular and Mitochondrial Diseases Presenting with Different Cardiomyopathy Phenotypes.

Cardiomyopathies are mostly determined by genetic mutations affecting either cardiac muscle cell structure or function. Nevertheless, cardiomyopathies may also be part of complex clinical phenotypes in the spectrum of neuromuscular (NMD) or mitochondrial diseases (MD). The aim of this study is to describe the clinical, molecular, and histological characteristics of a consecutive cohort of patients with cardiomyopathy associated with NMDs or MDs referred to a tertiary cardiomyopathy clinic. Consecutive patients with a definitive diagnosis of NMDs and MDs presenting with a cardiomyopathy phenotype were described. Seven patients were identified: two patients with ACAD9 deficiency (Patient 1 carried the c.1240C>T (p.Arg414Cys) homozygous variant in ACAD9; Patient 2 carried the c.1240C>T (p.Arg414Cys) and the c.1646G>A (p.Ar549Gln) variants in ACAD9); two patients with MYH7-related myopathy (Patient 3 carried the c.1325G>A (p.Arg442His) variant in MYH7; Patient 4 carried the c.1357C>T (p.Arg453Cys) variant in MYH7); one patient with desminopathy (Patient 5 carried the c.46C>T (p.Arg16Cys) variant in DES); two patients with mitochondrial myopathy (Patient 6 carried the m.3243A>G variant in MT-TL1; Patient 7 carried the c.253G>A (p.Gly85Arg) and the c.1055C>T (p.Thr352Met) variants in MTO1). All patients underwent a comprehensive cardiovascular and neuromuscular evaluation, including muscle biopsy and genetic testing. This study described the clinical phenotype of rare NMDs and MDs presenting as cardiomyopathies. A multidisciplinary evaluation, combined with genetic testing, plays a main role in the diagnosis of these rare diseases, and provides information about clinical expectations, and guides management.

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.

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.

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.

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.

Chest Dynamic MRI as Early Biomarker of Respiratory Impairment in Amyotrophic Lateral Sclerosis Patients: A Pilot Study.

Background: Amyotrophic lateral sclerosis (ALS) is a neuromuscular progressive disorder characterized by limb and bulbar muscle wasting and weakness. A total of 30% of patients present a bulbar onset, while 70% have a spinal outbreak. Respiratory involvement represents one of the worst prognostic factors, and its early identification is fundamental for the early starting of non-invasive ventilation and for the stratification of patients. Due to the lack of biomarkers of early respiratory impairment, we aimed to evaluate the role of chest dynamic MRI in ALS patients. Methods: We enrolled 15 ALS patients and 11 healthy controls. We assessed the revised ALS functional rating scale, spirometry, and chest dynamic MRI. Data were analyzed by using the Mann-Whitney U test and Cox regression analysis. Results: We observed a statistically significant difference in both respiratory parameters and pulmonary measurements at MRI between ALS patients and healthy controls. Moreover, we found a close relationship between pulmonary measurements at MRI and respiratory parameters, which was statistically significant after multivariate analysis. A sub-group analysis including ALS patients without respiratory symptoms and with normal spirometry values revealed the superiority of chest dynamic MRI measurements in detecting signs of early respiratory impairment. Conclusions: Our data suggest the usefulness of chest dynamic MRI, a fast and economically affordable examination, in the evaluation of early respiratory impairment in ALS patients.

The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study.

BACKGROUND: Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. METHODS: The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. CONCLUSIONS: The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

Nutritional support and prevention of post-intensive care syndrome: the Italian SIAARTI survey.

BACKGROUND: Malnutrition and muscle wasting are common in ICU patients and predict adverse patient-centered outcomes. The Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) conducted a nationwide survey to identify the nutritional practices in the Italian ICUs and to plan future, training interventions to improve the national clinical practice. METHODS: Nationwide online survey, involving Italian ICUs, developed by experts affiliated with SIAARTI. Invitations to participate were distributed through emails and social networks. Data were collected over a period of three months (October 1 to December 31, 2022) during 2022. RESULTS: One hundred full responses from participating ICUs were collected. The number of beds is < 10 in most ICUs and > 20 in 11 ICUs. Most ICUs (87%) are mixed, cardiac (5%), neurosurgical (4%), or pediatric ICUs (1%). Although the nutritional program is widely prescribed based on the patients' general evaluation, 52 ICUs (52%) do not perform nutritional risk evaluation at admission in case of > 24-h stay. Daily caloric intake is mainly based on the 25 kcal/kg equation; otherwise, the Harris-Benedict formula is mostly used, whereas indirect calorimetry is less used. Most clinicians apply a personalized nutritional approach to organ failure. Most ICUs have a nutritional management protocol, and enteral nutrition (EN) is frequently started within 2 days from admission, while supplemental parenteral nutrition is used when EN is insufficient by most clinicians. The EN administered seems to correspond to that prescribed, but it is stopped if the gastric residual gastric is > 300-500 ml in most ICUs. CONCLUSION: Prescription, route, and mode of administration of nutritional support seem to be in line with international recommendations, while suggestions on the tools for assessing the nutritional risk and monitoring efficacy and complications seem far less followed. Future national clinical studies are necessary to investigate the optimal nutritional and metabolic management of critically ill patients and the correspondence with the results of this survey on actual practices.

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.

Extracorporeal blood purification therapies for sepsis-associated acute kidney injury in critically ill patients: expert opinion from the SIAARTI-SIN joint commission.

Sepsis-Associated Acute Kidney Injury is a life-threatening condition leading to high morbidity and mortality in critically ill patients admitted to the intensive care unit. Over the past decades, several extracorporeal blood purification therapies have been developed for both sepsis and sepsis-associated acute kidney injury management. Despite the widespread use of extracorporeal blood purification therapies in clinical practice, it is still unclear when to start this kind of treatment and how to define its efficacy. Indeed, several questions on sepsis-associated acute kidney injury and extracorporeal blood purification therapy still remain unresolved, including the indications and timing of renal replacement therapy in patients with septic vs. non-septic acute kidney injury, the optimal dialysis dose for renal replacement therapy modalities in sepsis-associated acute kidney injury patients, and the rationale for using extracorporeal blood purification therapies in septic patients without acute kidney injury. Moreover, the development of novel extracorporeal blood purification therapies, including those based on the use of adsorption devices, raised the attention of the scientific community both on the clearance of specific mediators released by microorganisms and by injured cells and potentially involved in the pathogenic mechanisms of organ dysfunction including sepsis-associated acute kidney injury, and on antibiotic removal. Based on these considerations, the joint commission of the Italian Society of Anesthesiology and Critical Care (SIAARTI) and the Italian Society of Nephrology (SIN) herein addressed some of these issues, proposed some recommendations for clinical practice and developed a common framework for future clinical research in this field.

Regional citrate anticoagulation (RCA) in critically ill patients undergoing renal replacement therapy (RRT): expert opinion from the SIAARTI-SIN joint commission.

Renal replacement therapies (RRT) are essential to support critically ill patients with severe acute kidney injury (AKI), providing control of solutes, fluid balance and acid-base status. To maintain the patency of the extracorporeal circuit, minimizing downtime periods and blood losses due to filter clotting, an effective anticoagulation strategy is required.Regional citrate anticoagulation (RCA) has been introduced in clinical practice for continuous RRT (CRRT) in the early 1990s and has had a progressively wider acceptance in parallel to the development of simplified systems and safe protocols. Main guidelines on AKI support the use of RCA as the first line anticoagulation strategy during CRRT in patients without contraindications to citrate and regardless of the patient's bleeding risk.Experts from the SIAARTI-SIN joint commission have prepared this position statement which discusses the use of RCA in different RRT modalities also in combination with other extracorporeal organ support systems. Furthermore, advise is provided on potential limitations to the use of RCA in high-risk patients with particular attention to the need for a rigorous monitoring in complex clinical settings. Finally, the main findings about the prospective of optimization of RRT solutions aimed at preventing electrolyte derangements during RCA are discussed in detail.

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.