Safety and efficacy of ketorolac continuous infusion for multimodal analgesia of vaso-occlusive crisis in patients with sickle cell disease.

Pain is an hallmark of sickle-cell-related acute clinical manifestations as part of acute vaso-occlusive crisis (VOC). In SCD pain has different origins such as vascular or neuropathic pain, which requires multimodal analgesia. This is based on the administration of drugs with different pharmacological mechanisms of action, maximizing analgesia and minimizing their adverse events and the risk of drug-addition in patients experiencing acute-recurrent pain events as in SCD. Ketorolac is a potent non-narcotic analgesic, being relatively safe and effective during pain-management in children and adults. Up to now, there is a lack of safety information on continuous infusion ketorolac as used to control acute pain in patients with SCD, and the benefits/risks ratio needs to be investigated. Here, we report for the first time the safety profile of ketorolac in the special population of patients with SCD. We confirmed that ketorolac in combination with tramadol, an opioid like molecule, is effective in pain control of adult patients with SCD experiencing acute severe VOCs defined by pain visual analog scale. Our study shows that short term (72 h) continuous infusion of ketorolac plus tramadol is not associated with adverse events such as liver or kidney acute disfunction or abnormalities in coagulation parameters during patients' hospitalization and within 30 days after patients discharge. This is extremely important for patients with SCD, who should have access to multimodal therapy to control recurrent acute pain crisis in order to limit central sensitization a fearsome issue of undertreated recurrent acute pain and of chronic pain.

The role of beta-blocker drugs in critically ill patients: a SIAARTI expert consensus statement.

BACKGROUND: The role of ß-blockers in the critically ill has been studied, and data on the protective effects of these drugs on critically ill patients have been repeatedly reported in the literature over the last two decades. However, consensus and guidelines by scientific societies on the use of ß-blockers in critically ill patients are still lacking. The purpose of this document is to support the clinical decision-making process regarding the use of ß-blockers in critically ill patients. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient's care process. METHODS: The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) selected a panel of experts and asked them to define key aspects underlying the use of ß-blockers in critically ill adult patients. The methodology followed by the experts during this process was in line with principles of modified Delphi and RAND-UCLA methods. The experts developed statements and supportive rationales in the form of informative text. The overall list of statements was subjected to blind votes for consensus. RESULTS: The literature search suggests that adrenergic stress and increased heart rate in critically ill patients are associated with organ dysfunction and increased mortality. Heart rate control thus seems to be critical in the management of the critically ill patient, requiring careful clinical evaluation aimed at both the differential diagnosis to treat secondary tachycardia and the treatment of rhythm disturbance. In addition, the use of ß-blockers for the treatment of persistent tachycardia may be considered in patients with septic shock once hypovolemia has been ruled out. Intravenous application should be the preferred route of administration. CONCLUSION: ß-blockers protective effects in critically ill patients have been repeatedly reported in the literature. Their use in the acute treatment of increased heart rate requires understanding of the pathophysiology and careful differential diagnosis, as all causes of tachycardia should be ruled out and addressed first.

Exploring Outcome Priorities and Real-Life Management of Chemotherapy-Induced Peripheral Neurotoxicity: A Survey of the Italian Association for the Study of Pain members.

Introduction: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects nearly 70% of cancer patients after chemotherapy, causing sensory, motor, autonomic dysfunction, and neuropathic pain. The Desirability of Outcome Ranking (DOOR) framework is proposed as a better way to assess preventive or therapeutic interventions for CIPN. Methods: A survey was conducted among Italian healthcare professionals and researchers affiliated to the Italian Chapter of the International Association for the Study of Pain (AISD) to identify the most important outcomes in clinical management and research. Results: Among the 73 respondents, 61 qualified for the survey, with an overall response rate of 1.2%. The vast majority were physicians (77%), most of whom were anesthesiologists (47.5%). The results showed that pain, survival, sensory impairment, motor impairment, and quality of life were consistently ranked as the most important outcomes, but there was significant disagreement in the outcomes relative ranking, making it difficult to develop a DOOR algorithm. The study also revealed that clinicians commonly use structured interviews to evaluate patients with CIPN, and the most prescribed drugs or supplements were palmitoylethanolamide, pregabalin, gabapentin and alpha lipoic acid as preventive agents and pregabalin, palmitoylethanolamide, duloxetine, gabapentin, and amitriptyline as therapeutic agents. However, many of these drugs have not been clinically proven to be effective for CIPN. Discussion: This study suggests that the implementation of a DOOR framework for CIPN using healthcare professionals is more difficult than expected, given the significant disagreement in our respondents' ranking of outcomes. Our work provides interesting topics for future research in CIPN, but its limitations include a small sample size, a low response rate, and a possible selection bias.

Pulmonary Vasodilator and Inodilator Drugs in Cardiac Surgery: A Systematic Review With Bayesian Network Meta-Analysis.

OBJECTIVE: The authors performed a systematic review to evaluate the effect of pharmacologic therapy on pulmonary hypertension in the perioperative setting of elective cardiac surgery (PROSPERO CRD42023321041). DESIGN: Systematic review of randomized controlled trials with a Bayesian network meta-analysis. SETTING: The authors searched biomedical databases for randomized controlled trials on the perioperative use of inodilators and pulmonary vasodilators in adult cardiac surgery, with in-hospital mortality as the primary outcome and duration of ventilation, length of stay in the intensive care unit, stage 3 acute kidney injury, cardiogenic shock requiring mechanical support, and change in mean pulmonary artery pressure as secondary outcomes. PARTICIPANTS: Twenty-eight studies randomizing 1,879 patients were included. INTERVENTIONS: Catecholamines and noncatecholamine inodilators, arterial pulmonary vasodilators, vasodilators, or their combination were considered eligible interventions compared with placebo or standard care. MEASUREMENTS AND MAIN RESULTS: Ten studies reported in-hospital mortality and assigned 855 patients to 12 interventions. Only inhaled prostacyclin use was supported by a statistically discernible improvement in mortality, with a number-needed-to-treat estimate of at least 3.3, but a wide credible interval (relative risk 1.26 × 10-17 - 0.7). Inhaled prostacyclin and nitric oxide were associated with a reduction in intensive care unit stay, and none of the included interventions reached a statistically evident difference compared to usual care or placebo in the other secondary clinical outcomes. CONCLUSIONS: Inhaled prostacyclin was the only pharmacologic intervention whose use is supported by a statistically discernible improvement in mortality in the perioperative cardiac surgery setting as treatment of pulmonary hypertension. However, available evidence has significant limitations, mainly the low number of events and imprecision.

The Great pretender: the first case of septic shock due to Capnocytophaga canimorsus in Sardinia. A Case report and review of the literature.

Capnocytophaga canimorsus (C. canimorsus) is an emerging pathogen in critical care. C. canimorsus is a Gram-negative bacillus, commonly isolated as a commensal microorganism of the oral flora of healthy dogs and cats. A 63-year-old woman came to the emergency department with fever, chills, and malaise 2 days after a minor dog bite. After admission to the medicine ward, she developed respiratory failure and livedo reticularis. In the intensive care unit (ICU), she presented full-blown septic shock with thrombocytopenia, coagulopathy, severe acute kidney injury, and liver injury. We describe the first case of septic shock with Multiple Organ Dysfunction Syndrome related to Capnocytophaga canimorsus infection in Sardinia and its treatment in a tertiary hospital ICU. We also review recent literature on the relevance of C. canimorsus in human disease and critical illness.

Metabolomics and Microbiomics: New Potential Strategies in Chronic Pain Syndrome.

Chronic pain affects almost 20% of the European adult population and it significantly reduces patients' quality of life. Chronic pain is considered a multidimensional experience determined by the interaction of several genetic and environmental factors. The effect of specific genetic contributions is often unclear, and the interpretation of the results from studies focused on genetic influences on pain has been complicated by the existence of multiple pain phenotypes. A step forward from genetics could be given by the application of metabolomics and microbiomics tools. Metabolomics is a powerful approach for hypothesis generation in biology, and it aims to analyze low molecular weight compounds, either metabolic intermediates or metabolic end-products, resulting from human or microbial metabolism. Microbiomics is a fast-growing field in which all the microbes are examined together, and as a result, its perturbation may indicate the development of chronic diseases. By applying these methodologies for the study of chronic pain, several differences have been identified. The alteration of the choline-PAF pathway is an intriguing finding recognized by several groups. In our opinion, metabolomics and microbiomics techniques will allow significant progress into the medical field. Patients may benefit from the possibility of being stratified and classified based on their metabolic and microbial profile, which, in the next future, may lead to personalized therapy.

Clinical practice recommendations on the management of perioperative cardiac arrest: A report from the PERIOPCA Consortium.

BACKGROUND: Perioperative cardiac arrest is a rare complication with an incidence of around 1 in 1400 cases, but it carries a high burden of mortality reaching up to 70% at 30 days. Despite its specificities, guidelines for treatment of perioperative cardiac arrest are lacking. Gathering the available literature may improve quality of care and outcome of patients. METHODS: The PERIOPCA Task Force identified major clinical questions about the management of perioperative cardiac arrest and framed them into the therapy population [P], intervention [I], comparator [C], and outcome [O] (PICO) format. Systematic searches of PubMed, Embase, and the Cochrane Library for articles published until September 2020 were performed. Consensus-based treatment recommendations were created using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The strength of consensus among the Task Force members about the recommendations was assessed through a modified Delphi consensus process. RESULTS: Twenty-two PICO questions were addressed, and the recommendations were validated in two Delphi rounds. A summary of evidence for each outcome is reported and accompanied by an overall assessment of the evidence to guide healthcare providers. CONCLUSIONS: The main limitations of our work lie in the scarcity of good quality evidence on this topic. Still, these recommendations provide a basis for decision making, as well as a guide for future research on perioperative cardiac arrest.

Basic guide to chronic pain assessment: from neurophysiology to bedside.

Chronic musculoskeletal pain is a highly prevalent condition that is commonly encountered in both general and specialist practice. Nonetheless, it still represents a significant challenge to the practitioners because of the lack of substantial evidence-based guidance. This review aimed to summarize the main pathophysiological mechanisms of chronic pain offering a mechanism-oriented approach to diagnosis and management. We believe that a basic knowledge of the physical signs and symptoms of these mechanisms could empower the clinician to choose appropriate medication and identify high-risk pain patients. Central sensitization and neuropathic features may arise in previously nociceptive and inflammatory pain syndromes. Central sensitization is a functional remodeling of the spinal cord, where light touch afferents are recruited by nociceptive second-order neurons. Neuropathic features include both negative signs, such as reduced perception of vibration and touch, and positive symptoms, such as paroxysmal electric shock pain, due to ectopic discharge. These phenomena are the neurobiological basis of the commonly defined refractory chronic pain. Early detection and specific treatment of these mechanisms are required in order to restrain the reinforcement of pronociceptive remodeling of the nervous system.

Nurses' Behavior Regarding Pain Treatment in an Emergency Department: A Single-Center Observational Study.

PURPOSE: The aim of this prospective study was to assess the behavior of emergency department (ED) nurses with regard to pain and their role in pain management in a real-life clinical setting. METHODS: A total of 509 consecutive patients were enrolled during a 6-week period. A case-report form was used to collect data on nurses' approaches to pain, time to analgesia provision, and patient-perceived quality of analgesia. RESULTS: Triage nurses actively inquired about pain in almost every case, but they did not estimate pain intensity in a third of patients. In the majority of cases, triage nurses did not report pain-related findings to the physician, who was the only professional that could prescribe analgesia to patients. The assignment of the color-coding of triage by nurses appears to be related to the perceived severity of the clinical case and a more comprehensive evaluation of pain. More than half of patients were at least fairly satisfied with analgesia. CONCLUSION: Pain is increasingly screened during triage, but its comprehensive assessment and management still lack systematic application. We believe that further education and implementation of analgesia protocols may empower nurses to manage ED patients' pain more effectively and in a more timely manner.

Compassion fatigue, watching patients suffering and emotional display rules among hospice professionals: a daily diary study.

BACKGROUND: Hospice workers are required to regularly use emotional regulation strategies in an attempt to encourage and sustain terminally ill patients and families. Daily emotional regulation in reaction to constantly watching suffering patients may be intensified among those hospice professionals who have high levels of compassion fatigue. The main object of this study was to examine the relationship between daily exposition to seeing patient suffering and daily emotional work, and to assess whether compassion fatigue (secondary traumatic stress and burnout) buffers this relationship. METHODS: We used a diary research design for collecting daily fluctuations in seeing patients suffering and emotional work display. Participants filled in a general survey and daily survey over a period of eight consecutive workdays. A total of 39 hospice professionals from two Italian hospices participated in the study. RESULTS: Multilevel analyses demonstrated that daily fluctuations in seeing patients suffering was positively related to daily emotional work display after controlling for daily death of patients. Moreover, considering previous levels of compassion fatigue, a buffering effect of high burnout on seeing patients suffering - daily emotional work display relationship was found. CONCLUSIONS: A central finding of our study is that fluctuations in daily witness of patients suffering are positively related to daily use of positive emotional regulations. Further, our results show that burnout buffers this relationship such that hospice professionals with high burnout use more emotional display in days where they recurrently witness patients suffering.

Stress among university students: factorial structure and measurement invariance of the Italian version of the Effort-Reward Imbalance student questionnaire.

BACKGROUND: In the last decade academic stress and its mental health implications amongst university students has become a global topic. The use of valid and theoretically-grounded measures of academic stress in university settings is crucial. The aim of this study was to examine the factorial structure, reliability and measurement invariance of the short student version of the effort-reward imbalance questionnaire (ERI-SQ). METHODS: A total of 6448 Italian university students participated in an online cross-sectional survey. The factorial structure was investigated using exploratory factor analysis and confirmatory factor analysis. Finally, the measurement invariance of the ERI-SQ was investigated. RESULTS: Results from explorative and confirmatory factor analyses showed acceptable fits for the Italian version of the ERI-SQ. A modified version of 12 items showed the best fit to the data confirming the 3-factor model. Moreover, multigroup analyses showed metric invariance across gender and university course (health vs other courses). CONCLUSIONS: In sum, our results suggest that the ERI-SQ is a valid, reliable and robust instrument for the measurement of stress among Italian university students.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality.

OBJECTIVE: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: Two hundred fifty-one physicians from 46 countries. INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality.

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.

Long-term, prolonged-release oral tapentadol for the treatment of refractory chronic low back pain: a single-center, observational study.

BACKGROUND: Chronic back pain is a leading cause of disability worldwide and it is still inadequately treated. Tapentadol is a dual-acting analgesic drug µ-opioid receptor (MOR) agonist/norepinephrine reuptake inhibitor, carrying a lower risk for opioid withdrawal symptoms and opioid-related adverse effects in comparison to potent opioid drugs. This study investigates the effectiveness, safety and tolerability of the prolonged release oral formulation of tapentadol (tapentadol PR) in 27 patients affected by refractory chronic low back pain during a long-term follow-up (up to 51 months). METHODS: This is an observational study conducted at the Pain Therapy and Palliative Care Unit of University Hospital of Cagliari, Italy. We enrolled 27 patients affected by chronic low back pain refractory to other pharmacological treatments according to the inclusion criteria. We prospectively evaluated oral tapentadol PR therapy during a long-term follow-up (up to 51 months) according to the following outcomes: pain intensity during the previous 72 hours (Numeric Rating Scale 3), quality of life (Short Form-12 Health Survey), self-reported treatment effectiveness (Patient Global Impression of Change scale), physician evaluation of treatment effectiveness (Clinician Global Impression of Change scale), treatment-related adverse effects, reason for tapentadol therapy interruption and tapentadol dosage. RESULTS: All the patients reported a significant improvement of pain intensity and quality of life at the last follow-up. CONCLUSIONS: These results show the long-term effectiveness, safety and tolerability of oral tapentadol PR for the treatment of refractory chronic low back pain in a real-life clinical setting.

Steroids and Survival in Critically Ill Adult Patients: A Meta-analysis of 135 Randomized Trials.

OBJECTIVE: Corticosteroids have important effects on intermediate outcomes in critically ill patients, but their effect on survival is unknown. The objective of this meta-analysis was to analyze the effect on mortality of corticosteroids in critical and perioperative settings. DESIGN: A meta-analysis of randomized trials. SETTING: PubMed, Embase, BioMed Central, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched to February 1, 2018, for randomized trials comparing corticosteroids with placebo or standard care. PARTICIPANTS: Critically ill or surgical adult patients. INTERVENTIONS: Corticosteroids compared with placebo or standard care. MEASUREMENTS AND MAIN RESULTS: A total of 44,553 patients from 135 studies were included. Overall, mortality in the corticosteroid group and in the control group were similar (16% v 16%; p = 0.9). Subanalyses identified a beneficial effect of corticosteroids on survival in patients with respiratory system diseases (9% v 13%; p < 0.001) and bacterial meningitis (28% v 32%; p= 0.04), and a detrimental effect on survival in patients with traumatic brain injury (22% v 19%; p < 0.001). No differences in mortality were found in patients with cardiac diseases (7% v 6%; p = 0.7), in patients undergoing cardiac surgery (2.8% v 3.2% p = 0.14), and when treatment duration or patient age were considered. CONCLUSIONS: This meta-analysis documents the safety of corticosteroids in the overall critically ill population with the notable exception of brain injury patients, a setting where the authors confirmed their detrimental effect on survival. A possible beneficial effect of corticosteroids on survival was found among patients with respiratory diseases and in patients with bacterial meningitis.

Nitric Oxide in Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To investigate the efficacy and safety of perioperative administration of nitric oxide in cardiac surgery. DESIGN: Meta-analysis of randomized controlled trials (RCTs). PARTICIPANTS: Cardiac surgery patients. INTERVENTIONS: A search of Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE for RCTs that compared nitric oxide with placebo or other comparators. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intensive care unit (ICU) stay, and secondary outcomes were mortality, duration of mechanical ventilation, and reduction of mean pulmonary artery pressure. The study included 18 RCTs comprising 958 patients. The authors calculated the pooled odds ratio (OR) and the mean difference (MD) with random-effects model. Quantitative synthesis of data demonstrated a clinically negligible reduction in the length of ICU stay (MD -0.38 days, confidence interval CI [-0.65 to -0.11]; p = 0.005) and mechanical ventilation duration (MD -4.81 hours, CI [-7.79 to -1.83]; p = 0.002) compared with all control interventions with no benefit on mortality. CONCLUSIONS: Perioperative delivery of inhaled nitric oxide resulted to be of no or minimal benefit in patients with pulmonary hypertension undergoing cardiac surgery. Large, randomized trials are needed to further assess its effect on major clinical outcomes and its cost-effectiveness.

Healthcare-associated respiratory infections in intensive care unit can be reduced by a hand hygiene program: A multicenter study.

PURPOSE: Healthcare-associated respiratory tract infections are common and markedly affect the quality of life and mortality, as well as increasing costs for health systems due to prolonged hospitalisation. This study aimed to assess the change in both level and trend of respiratory tract infections after a specific hand hygiene program for intensive care unit (ICU) staff. MATERIALS AND METHODS: The infection data collection was carried out from January 2013 to August 2014. The hand hygiene program started in December 2013. To analyse the change in level and trend of infections after the intervention, the Interrupted Time Series method was used. Chi-square test was used to compare the incidence of respiratory tract infections before and after the intervention. RESULTS: A total of 825 patients were hospitalised in three Italian ICUs. The infection level was significantly decreased by 36.3 infections per 1000 device-days after the intervention. The infection trend was also decreased of about 1 infection per month. CONCLUSIONS: After the hand hygiene program a decreased level of infection was found. Continuous performance feedback should be provided to promote a long-term adherence to the guidelines. Organisational and individual risk factors must be individuated and correctly managed to increase quality of practice.

An innovative technique to improve safety of volatile anesthetics suction from the cardiopulmonary bypass circuit.

CONTEXT: Myocardial injury during cardiac surgery on cardiopulmonary bypass (CPB) is a major determinant of morbidity and mortality. Preclinical and clinical evidence of dose- and time-related cardioprotective effects of volatile anesthetic drugs exist and their use during the whole surgery duration could improve perioperative cardiac protection. Even if administering volatile agents during CPB are relatively easy, technical problems, such as waste gas scavenging, may prevent safe and manageable administration of halogenated vapors during CPB. AIMS: The aim of this study is to improve the safe administration of volatile anesthesia during CPB. SETTINGS AND DESIGN: Tertiary teaching hospital. SUBJECTS AND METHODS: We describe an original device that collects and disposes of any volatile anesthetic vapors present in the exit stream of the oxygenator, hence preventing its dispersal into the operating theatre environment and adaptively regulates pressure of oxygenator chamber in the CPB circuit. RESULTS: We have so far applied a prototype of this device in more than 1300 adult cardiac surgery patients who received volatile anesthetics during the CPB phase. CONCLUSIONS: Widespread implementation of scavenging system like the one we designed may facilitate the perfusionist and the anesthesiologist in delivering these cardioprotective drugs with beneficial impact on patients' outcome without compromising on safety.