INTRODUCTION:Cardiopulmonary bypass has been used to perform complex cardiac surgery for over 70 years. Advances in bypass techniques and perioperative medicine have increased the safety of cardiac procedures, leading to reduced morbidity and mortality. Nevertheless, cardiopulmonary bypass still carries risks, including systemic inflammation and dysfunction of various organs. To date, optimal blood pressure management during cardiopulmonary bypass remains a subject of ongoing debate. Conflicting evidence exists regarding negative outcomes associated with both low and high mean arterial pressures. Current clinical guidelines recommend a broad target range for mean arterial pressure during cardiopulmonary bypass, which underscores the existing gap in knowledge. In non-cardiac surgery, the time-weighted average of mean arterial pressure has been used to determine minimum safe thresholds, with greater deviation from 65 mm Hg associated with an increased risk of adverse outcomes. However, the definition and reporting of low blood pressure during cardiopulmonary bypass varies between studies, and the use of time-weighted averages below the threshold is still uncommon. Details on pump flow during extracorporeal circulation are seldom reported. METHODS AND ANALYSIS:We plan to conduct a retrospective, single-centre data analysis to investigate the effects of both arterial blood pressure and extracorporeal pump flow, including their time-weighted averages and areas under defined thresholds, during cardiopulmonary bypass on neurological outcomes in adult patients undergoing cardiac surgery between 2014 and 2023. The study will include both elective and emergency procedures, with separate analyses conducted based on the urgency and complexity of the operations. Digitally recorded anaesthesia and perfusion records will be imported and validated to extract information on haemodynamic parameters, neurological monitoring and extracorporeal circulation. Ischaemic and haemorrhagic strokes will be identified by screening postoperative brain imaging records for keywords indicating neurological events. Diagnostic data and additional patient and procedural information will be extracted from the local cardiac surgery database and hospital information system. Information about incidence and course of postoperative delirium will be extracted from the patient data management system used in intensive care. We expect to include approximately 500-700 cases per year in the final analysis. ETHICS AND DISSEMINATION:The local ethics committee approved our study (Ethics Committee of the Medical University of Graz, IRB00002556, 36-296 ex 23/24). We aim to publish the results of our study preferably in an open access format. TRIAL REGISTRATION NUMBER:The study protocol was registered at the Center for Open Science (https://doi.org/10.17605/OSF.IO/FAMV3).

Background: Post-intensive care syndrome encompasses physical, cognitive, and psychological impairments that persist in patients after discharge from an intensive care unit. There is considerable variation in the tools used for assessment. This systematic review aimed to summarize the consensus-based recommendations for assessing post-intensive care syndrome. Methods: A comprehensive literature search identified four consensus-based guidelines. A quality assessment carried out using the Appraisal of Guidelines for Research and Evaluation II tool demonstrated high methodological standards across all the included papers. Results: The guidelines consistently emphasize assessing cognition, mental health, and physical function as the core domains. However, there are notable differences in the specific tools recommended. Major et al. focused on physical examinations, while Mikkelsen et al. proposed a fundamental package of five tools covering the key domains. Spies et al. aimed for a pragmatic set of freely available instruments administrable within 30 min. Nakanishi et al. provided a detailed ranking of instruments for each domain. The availability of validated translations varied considerably across languages. Some tools developed specifically for post-intensive care syndrome were not considered by any consensus conference. Conclusions: Further work is needed to establish a universally accepted standard for assessing post-intensive care syndrome that considers practical implementation across diverse settings and languages.

BACKGROUND:Anaesthesia contributes to greenhouse gas emissions and can play a crucial role in reducing the carbon footprint of the global healthcare sector. The aim of this systematic review is to identify which departmental interventions influence estimated carbon dioxide (CO2) equivalent emissions of anaesthesia and to quantify their reductions. METHODS:A systematic literature search was conducted through four major electronic databases (Cochrane Library, Embase, MEDLINE, and PubMed) for studies investigating the changes in CO2 equivalent emissions per anaesthetic before and after departmental green anaesthesia interventions. Data were extracted by two independent reviewers. The primary outcomes were mean decrease of CO2 equivalents in kilograms per anaesthetic and total decrease in CO2 equivalents in tonnes. The mean effect was calculated as percentage change per patient and in total. RESULTS:Of 3987 screened studies, 13 met the criteria for quantitative synthesis and showed low to moderate risk of bias. The following types of departmental sustainability interventions were found: education of staff, decreased use of desflurane and sevoflurane, promotion of TIVA, use of low fresh gas flows, proper waste management, and formation of green teams. The postinterventional total mean decrease of CO2 equivalents in kilograms per anaesthetic was 68.2% (18.6%) and in total tonnes was 75.2% (16.3%). CONCLUSIONS:Our analysis demonstrates the substantial CO2 reduction potential inherent in sustainable anaesthesia programmes. Currently available literature supports staff education on avoidance of desflurane, reduction of volatile anaesthesia, lower fresh gas flow, increased utilisation of TIVA, and implementation of proper waste management protocols in operating rooms as potentially effective interventions.

Effective postoperative pain management is crucial for patient recovery and satisfaction. Smoking may impact pain perception and analgesic requirements, but its effects on postoperative opioid needs remain unclear. The objective of this study was to determine whether patients who smoke have different postoperative opioid requirements compared to nonsmokers in the first 24 and 48 h after surgery. We conducted a systematic review and meta-analysis of studies comparing postoperative opioid use between smokers and nonsmokers. A comprehensive literature search was performed in Web of Science and PubMed databases. Opioid doses were converted to morphine equivalents for comparison. Random effects meta-analysis was used to calculate pooled effect sizes. Eight studies (784 patients) were included for the primary 24-h outcome and seven studies (1164 patients) for the 48-h outcome. Meta-analysis showed significantly higher opioid requirements in smokers compared to nonsmokers at both 24 h (standardized mean difference [SMD] 0.90, 95

BACKGROUND:Acute kidney injury (AKI) is a common complication after coronary artery bypass grafting (CABG), associated with adverse short- and long-term outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce occurrence of AKI in several populations, yet their perioperative effects in patients undergoing CABG are unknown. METHODS:We conducted a retrospective study at the Department of Cardiac Surgery, Medical University of Graz (2020-2024) to evaluate the impact of preoperative SGLT2i use on cardiac surgery-associated AKI in adults undergoing urgent or emergent isolated coronary artery bypass grafting in patients with an indication for SGLT2i therapy (type 2 diabetes mellitus, heart failure with reduced ejection fraction, or chronic kidney disease). Patients with preoperative dialysis, sepsis, reoperation, mechanical circulatory support or missing laboratory data were excluded. Exposure was defined as SGLT2i use within two weeks before surgery, and the primary outcome was cardiac surgery-associated AKI (CSA-AKI) according to KDIGO criteria. Secondary outcomes included kidney replacement therapy, ICU length of stay, 30-day mortality and postoperative diabetic ketoacidosis. Causal effects were estimated using entropy balancing. Results were reported as weighted risk differences, risk ratios, and adjusted mean differences, with time-to-event outcomes analyzed via weighted Cox models and Kaplan-Meier estimates. RESULTS:Among 484 patients, 135 were on SGLT2i. CSA-AKI occurred in 23.0 % of SGLT2i users vs. 28.1 % of non-users (risk ratio of 0.63 [95 % CI 0.44-0.91; p = 0.014]). The association was pronounced in patients with heart failure with reduced ejection fraction and those with high EuroSCORE II. No differences were observed in other secondary endpoints and no cases of postoperative diabetic ketoacidosis occurred. CONCLUSION:Preoperative SGLT2i use was associated with a significantly lower risk of CSA-AKI in patients undergoing urgent or emergent CABG. These findings need to be confirmed in prospective multicenter trials but underline the favorable safety profile of this medication.

Chronic pain is a public health issue, leading to substantial healthcare costs and diminished quality of life for sufferers. While the role of anxiety in pain modulation has been extensively studied, the effects of other emotional states on the body’s pain control mechanisms remain less understood. This study sought to explore how different emotions (happiness, anger, sadness, and interest) affect conditioned pain modulation (CPM) and the wind-up phenomenon in healthy adults. This randomized controlled, cross-over trial involved 28 healthy participants aged 18–60. Participants watched video clips designed to induce specific emotions: happiness, anger, sadness, and interest. Emotional states were assessed using a 7-point Likert scale. Pain modulation was measured using CPM and the wind-up phenomenon. CPM was assessed with a hot water bath as the conditioning stimulus and pressure pain tolerance as the test stimulus. Wind-up was measured using pinprick needle stimulators and a visual analog scale. Data were analyzed using paired t tests to compare pre- and post-emotion induction values. Significant changes in emotional self-assessment values were observed for all emotions. Happiness increased CPM (4.6 ± 11.4, p = 0.04277), while sadness − 9.9 ± 23.1, p = 0.03211) and anger − 9.1 ± 23.3, p = 0.04804) decreased it. Interest did not significantly alter CPM (− 5.1 ± 25.8, p = 0.31042). No significant effects were found for the wind-up phenomenon across any emotional states. This study shows that emotional states significantly affect the body’s ability to modulate pain. Positive emotions like happiness enhance pain inhibition, while negative emotions such as sadness and anger impair it. These findings suggest that emotional modulation techniques could be integrated into pain management strategies to improve patient outcomes. Further research should explore a broader range of emotions and include objective measures to validate these results. Chronic pain is a widespread problem that affects millions of people and leads to high healthcare costs and decreased quality of life. Understanding how emotions impact pain can help us find better ways to manage it. This study looked at how different emotions (happiness, anger, sadness, and interest) affect the ability of the body to naturally control pain in healthy adults. Participants experienced different tests in a random order, like flipping a coin to decide the order. Each participant took part in all the tests to compare how different conditions affected them. We measured changes in their pain perception using two methods: conditioned pain modulation, which reflects how well the body can suppress pain after experiencing another painful stimulus, and the wind-up phenomenon, which measures how pain intensity increases with repeated stimulation. We found that emotions affected the body’s ability to control pain. Sadness and anger reduced the efficacy of conditioned pain modulation, making it harder for the body to reduce pain. Happiness improved CPM, enhancing the body’s natural ability to stop pain. Interest did not significantly change how pain was felt. We also did not find any significant changes in the wind-up phenomenon for any of the emotions tested. The results suggest that positive emotions like happiness can help reduce pain, while negative emotions like sadness and anger can make pain worse. This could lead to new pain management approaches that include methods to boost positive emotions and reduce negative ones.

The administration of opioids can be followed by enduring neuroplastic changes in the peripheral and central nervous systems. This remodeling can lead to opioid-induced hyperalgesia, causing an increased sensitivity to painful stimuli. The description of opioid-induced changes in the somatosensory system has seldom been described in the setting of opioid agonist therapy in the treatment of opioid use disorders, and the few existing reports provide no guidance with respect to the effect of varied doses or substances. The aim of the present study was to assess alterations of pain pathways among patients receiving opioid agonist therapy and to elucidate the dose-response relationship. This study was planned as cross-sectional in an outpatient clinic in Graz, Austria. Patients receiving opioid agonist therapy for opioid use disorders (including methadone, levomethadone, buprenorphine, and extended-release morphine) were asked to fill out a questionnaire, including the central sensitization inventory. A battery of somatosensory system assessments was then performed. A total of 120 patients participated (85 men/35 women). The mean oral morphine milligram equivalent (MME) was 694 ± 249 mg/day. Our study found significant alterations in pain perception, conditioned pain modulation, and wind-up. We demonstrated a moderate dose-response relationship between high-dose opioids and markers of central sensitization. The present trial demonstrates the clear effects of opioid agonist therapy on the somatosensory system. Both central sensitization and descending pain modulation are negatively affected by high doses of opioids and our data elucidate a moderate dose-response relationship for these phenomena.

Cluster headache is a severe and debilitating neurological condition characterized by intense, excruciating pain with a significant impact on patients' wellbeing. Although different treatment options are available, many patients continue to experience inadequate relief. Therefore, experimental strategies are increasingly studied. One of the more promising approaches is the use of ketamine. We present the currently available evidence and our own data. In this mixed-methods paper, we first summarize the available evidence of ketamine for treatment of cluster headache based on a systematic review of literature in MEDLINE, EMBASE and the Cochrane library of systematic reviews. As the level of evidence is quite limited, we report our own cohort study with ten patients treated with ketamine infusions for cluster headache. They were followed up to investigate the patients’ experience of treatment success and quality of life. The search and review of literature identified four reports with a total of 68 patients. All were uncontrolled case series. The current literature suggests that ketamine might decrease cluster headache. However, as the applied regimes and reported outcomes are highly heterogeneous, further analysis was futile. Our own data show high patient satisfaction with ketamine treatment. Despite the limited evidence, ketamine might be considered a potential therapeutic approach for cluster headache. Therefore, further research including randomized controlled trials should be encouraged. This article discusses the potential use of ketamine for the treatment of cluster headache, a severe neurological condition that can have a significant impact on patients' quality of life. The authors conducted a systematic review of the existing literature on ketamine for the treatment of cluster headache. Additionally, they also presented their own cohort study of ten patients receiving ketamine infusions. The review of the literature revealed four reports with a total of 68 patients, all of which were uncontrolled case series. While the current literature suggests that ketamine may be effective in relieving cluster headache symptoms, the heterogeneity of treatment regimens and reported outcomes makes it difficult to draw definitive conclusions. The authors' own cohort study found that patients were very satisfied with ketamine treatment, indicating a potential benefit of this approach. However, due to the limited evidence available, further research, including randomized controlled trials, is needed to better understand the efficacy of ketamine in the treatment of cluster headaches.

BACKGROUND:Photobiomodulation, also referred to as Low-Level Light Therapy (LLLT), has emerged as a promising intervention for pruritus, a prevalent and often distressing symptom. OBJECTIVES:This study investigated the efficacy of low-level light therapy (LLLT) in alleviating pruritus, hyperknesis, and alloknesis induced by histamine and Mucuna pruriens. METHODS:In a double-blind, randomized, sham-controlled trial with a split-body design, healthy volunteers underwent 6 minutes of LLLT and sham treatments in separate upper back quadrants. The histamine model was applied to the upper quadrants, and Mucuna pruriens to the lower quadrants. Pruritus intensity, alloknesis, hyperknesis, flare area, and skin temperature were measured pre and post treatment. RESULTS:Seventeen individuals (eight females, nine males) participated in the study. In the histamine model, LLLT notably reduced itch intensity (difference = 13.9 (95% CI: 10.5 - 17.4), p = 0.001), alloknesis (difference = 0.80 (95% CI: 0.58-1.02), p = 0.001), and hyperknesis (difference = 0.48 (95% CI: 0.09-0.86), p = 0.01). Skin temperature changes were not significantly different between the two groups (difference = -2.0 (95% CI: -6.7-2.6), p = 0.37). For the Mucuna pruriens model, no significant differences were observed in any measures, including itch intensity (difference = 0.8 (95% CI: -2.3 - 3.8), p = 0.61) hyperknesis (difference = 0.08 (95% CI: -0.06-0.33), p = 0.16) and alloknesis (difference = 0. 0.09 (95% CI: -0.08-0.256), p = 0.27). CONCLUSIONS:LLLT effectively reduced histamine-induced pruritus, alloknesis, and hyperknesis; however, LLLT was ineffective against Mucuna pruriens-induced pruritus. Further investigations are required to determine LLLT's effectiveness of LLLT in various pruritus models.

Delirium is a frequent complication in critically ill patients and is associated with adverse outcomes such as long-term cognitive impairment and increased mortality. It is unknown whether there are sex-related differences in intensive care unit (ICU) delirium and associated outcomes. We aimed to assess sex-specific differences in short-term mortality following ICU-delirium. We conducted a retrospective cohort study using the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Adult ICU patients who were diagnosed with delirium using the Confusion Assessment Method for the ICU (CAM-ICU) were included. The primary outcome was 30-day mortality following delirium onset. To control for baseline differences in demographics, illness severity, and comorbidities, we applied 1:1 propensity score matching. Cox proportional hazards regression models were used to evaluate the association between sex and mortality. A total of 8950 ICU patients with delirium were analyzed, of whom 42.6

Background: Cardiac arrest is the most time-sensitive medical condition, and survival probability is highly dependent on early, high-quality cardiopulmonary resuscitation (CPR) measures. Resuscitation registries are established tools for continuous quality improvement and serve as a source for research. Yet they lack comprehensive information on the quality of CPR measures themselves—such as the depth, rate, and release of chest compressions—and are limited in the temporal resolution of these measures. However, data on both are contained in the recordings of defibrillators. Aims: To develop a framework for healthcare providers to gain immediate case-specific feedback, reduce documentation efforts and make fine-grained information accessible for research. Approach: An open-source Python module named CPRDAT (Kern et al. Zenodo, https://doi.org/10.5281/zenodo.10057964) was designed. This module is capable of importing and extracting data from various defibrillators as well as data recorded by VitalRecorder ( VitalDB , Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Korea) into a uniform data object. Methods were implemented to automatically process, analyze, and aggregate these time-series of physiological signals, with particular attention to CPR. To reduce manual annotation workload, classification algorithms were developed. Plotting routines were developed to display the signals interactively in web applications, allowing healthcare providers to interact with the data through zooming, scaling, shifting, concatenating, merging and labelling. Results: The module was implemented into the German Resuscitation Registry, offering users a manufacturer-agnostic, data-driven, case-specific debriefing tool. Extracted information on CPR measures is stored in the registry. The framework, able to manage multiple time-series data sources, was further implemented in other settings, such as the analysis of laboratory data of a CPR swine model. Conclusions: The new module dramatically enhances the accessibility of physiologic time-series recordings. More fine-grained data will provide deeper insights into processes and CPR physiology. Finally, the open-source Python module abolishes barriers in research.

We thank Dr Chen et al. for their comments on our article on the effect of nociception level-guided anaesthesia on pain levels and opioid consumption in the post-anaesthesia care unit [1, 2]. Based on our meta-analysis, they conducted a trial sequential analysis to draw even deeper insights from previous studies. They showed that the current literature is not sufficient to conclusively assess the evidence. This important addendum strengthens our statement that, although there are currently studies that nociception level index-guided anaesthesia may reduce postoperative pain, they are not robust enough to recommend its general use. We strongly support the call for further research. However, it is also important to consider which population and procedures are included. It is possible that the nociception level index could be more useful in vulnerable patient groups (e.g. patients with chronic pain, chronic opioid use or anxiety) and interventions associated with severe postoperative pain. It is also important to take other factors into account in future studies. Does nociception level index-guided anaesthesia reduce the incidence of analgesic-induced adverse effects, such as postoperative nausea or cognitive deficit? How long would a potential difference in pain scores last? Is there a difference in chronic postoperative pain? In summary, the work of Chen et al. confirms our statement that we currently know too little about nociception level index-guided anaesthesia but that the current evidence raises interesting questions.

Acute postoperative pain remains a critical treatment priority and has prompted a search for technologies and techniques to assist with intra-operative analgesic monitoring and management. Anaesthetists traditionally rely on clinical judgement to guide intra-operative analgesia, but several emerging technologies such as the nociception level index herald the possibility of routine intra-operative analgesia monitoring. However, the impact of devices like nociception level index on postoperative outcomes has not been proven. We undertook a systematic review and meta-analysis of articles which compared nociception level index-guided analgesia to standard care. The primary outcomes were pain intensity and opioid consumption during the first 60-120 min after surgery. Secondary outcomes were the incidence of postoperative nausea and vomiting and duration of stay in the post-anaesthesia care unit. Ten studies, collectively including 662 patients and published between 2019 and 2023, met inclusion criteria for both the qualitative systematic review and quantitative meta-analysis. Risk of methodological bias was generally low or unclear, and six studies reported a significant conflict of interest relevant to their findings. Our meta-analysis was performed using a random-effects model. It found statistically significant benefits of nociception level index-guided analgesia for early postoperative pain (mean (95%CI) difference -0.46 (-0.88 to -0.03) on an 11-point scale, p = 0.03), and opioid requirement (mean (95%CI) difference -1.04 (-1.94 to -0.15) mg intravenous morphine equivalent, p = 0.02). Our meta-analysis of the current literature finds that nociception level index-guided analgesia statistically significantly reduces reported postoperative pain intensity and opioid consumption but fails to show clinically relevant outcomes. We found no evidence that nociception level index-guided analgesia affected postoperative nausea and vomiting nor duration of stay in the post-anaesthesia care unit.

Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has demonstrated utility in the treatment of neuropathic and inflammatory pain. Emerging reports have supported a possible role for its use in the treatment of chronic pain, although this remains controversial. We undertook a systematic review and meta-analysis to examine the efficacy of PEA as an analgesic agent for chronic pain. A systematic literature search was performed, using the databases MEDLINE and Web of Science, to identify double-blind randomized controlled trials comparing PEA to placebo or active comparators in the treatment of chronic pain. All articles were independently screened by two reviewers. The primary outcome was pain intensity scores, for which a meta-analysis was undertaken using a random effects statistical model. Secondary outcomes including quality of life, functional status, and side effects are represented in a narrative synthesis. Our literature search identified 253 unique articles, of which 11 were ultimately included in the narrative synthesis and meta-analysis. Collectively, these articles described a combined sample size of 774 patients. PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001). Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study. The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain. Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain.

Phantom limb pain (PLP) refers to pain perceived in a part of the body removed by amputation or trauma. Despite the high prevalence of PLP following amputation and the significant morbidity associated with it, robust therapeutic approaches are currently lacking. Calcitonin, a polypeptide hormone, has recently emerged as a novel analgesic with documented benefits in the treatment of several pain-related conditions. We present a systematic review that comprehensively evaluates the analgesic effects of calcitonin for patients with PLP. We searched MEDLINE, OLDMEDLINE, and PubMed Central databases with the key words "calcitonin” “phantom limb pain" and "phantom pain" to identify clinical studies evaluating the efficacy or effectiveness of calcitonin administration, in any form and dose, for the treatment of PLP. Additionally, Google Scholar was searched manually with the search term "calcitonin phantom limb pain". All four databases were searched from inception until 1 December 2022. The methodological quality of each included study was assessed using the Downs and Black checklist and the GRADE criteria were used to assess effect certainty and risk of bias. Our search identified 4108 citations, of which six ultimately met the criteria for inclusion in the synthesis. The included articles described a mix of open-label (n = 2), prospective observational cohort (n = 1), and randomized clinical trials (n = 3). The most common treatment regimen in the current literature is a single intravenous infusion of 200 IU salmon-derived calcitonin. The available evidence supported the use of calcitonin as either monotherapy or adjuvant therapy in the treatment of PLP during the acute phase, while the evidence surrounding calcitonin treatment in chronic PLP is heterogeneous. Given the limited treatment options for the management of PLP and calcitonin’s relatively wide therapeutic index, further research is warranted to determine the role that calcitonin may play in the treatment of PLP and other pain disorders.