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Poor preoperative sleep quality and impaired sleep continuity may heighten acute postoperative pain intensity and increase analgesic consumption, with negative implications for recovery, mental and physical health. The main objective of the current review was to investigate the relationship between preoperative sleep disturbance and acute postoperative pain control. Four electronic databases were systematically searched from inception to December 2023. Two reviewers screened articles, extracted data, and assessed risk of bias for each included study. The search identified 26 prospective cohort studies and 3 retrospective cohort studies (16104 participants). Of the 29 included studies, 23 focused on preoperative insomnia symptoms, and three studies each focused on preoperative objective sleep continuity or sleep-disordered breathing. Meta-analysis, based on five studies with 1226 participants, showed that clinically significant preoperative insomnia symptoms were associated with moderate to severe pain intensity on the first postoperative day (odds ratio 2.69 (95 % confidence interval 2.03–3.57), p < 0.0001). Qualitative analysis showed relatively robust associations between preoperative insomnia symptoms, impaired sleep continuity and poorer acute, as well as subacute, postoperative pain control. Findings related to obstructive sleep apnea syndrome were mixed. Given that insomnia is a potentially modifiable risk factor, interventions targeting sleep prior to surgery may improve postoperative pain control.

Background: Iontophoresis studies face challenges due to the unknown absolute drug dose delivered and the possible effect of the current used in drug delivery on the microvessels, known as current-induced vasodilation. This study aimed to investigate how various concentrations of acetylcholine (ACh), delivered through transdermal iontophoresis using repeated current pulses, impact the recovery profile of the microvascular response. Methods: The study included fifteen healthy volunteers, and microvascular responses to five concentrations of iontophorised ACh (ranging from 0.0055 mM to 55 mM) and sterile water were assessed at six forearm skin sites using polarized reflectance spectroscopy. Iontophoresis at each concentration involved three consecutive pulses separated 8 recovery periods. Results: Current-induced responses were more pronounced for lower concentrations of ACh and for sterile water. With repeated pulses, lower concentrations of ACh exhibited a recovery profile more akin to higher concentrations. Perspective: Through repeated iontophoresis of ACh, microvascular responses exhibit variation based on the drug concentration and the number of pulses administered. These variations are likely attributed to changes in skin conductivity and permeability.

Purpose: To assess changes of cerebral haemodynamic and intracranial pressure (ICP) in animals, with or without elevated ICP, during controlled haemorrhagic shock and resuscitation with Total REBOA (tREBOA). Method: In 22 anaesthetized and normoventilated pigs, after placement of catheters for monitoring invasive proximal blood pressure (pMAP), ICP, and vital parameters, and 60 min stabilisation phase, a controlled haemorrhagic shock (HS), was conducted. In 11 pigs (EICPG), an elevated ICP of 25–30 mmHg at the end HS was achieved by simulating an epidural mass. In 11 pigs (NICPG), the ICP was normal. tREBOA was then applied for 120 min. The changes of pMAP and ICP were followed, and cerebral perfusion pressure (CPP) calculated. The integrity of the autoregulation was estimated using a calculated Modified-Long Pressure Reactivity Index (mL-PRx). Results: After stabilisation, hemodynamics and physiological parameters were similar and normal in both groups. At the end of the HS, ICP was 16 mmHg in NICPG vs. 32 in EICPG (p = 0.0010). CPP was 30 mmHg in NICPG vs. 6 mmHg in EICPG (p = 0.0254). After aorta occlusion CPP increased immediately in both groups reaching after 15 min up to104 mmHg in NICPG vs. 126 mmHg in EICPG. Cerebrovascular reactivity seems to be altered during bleeding and occlusion phases in both groups with positive mL-PRx. The alteration was more pronounced in EICPG, but reversible in both groups. Conclusion: tREBOA is lifesaving by restoration the cerebral circulation defined as CPP in animals with HS with normal or elevated ICP. Despite the observation of short episodes of cerebral autoregulation impairment during the occlusion, mainly in EICPG, tREBOA seems to be an effective tool for improving cerebral perfusion in HS that extends the crucial early window sometimes known as the “golden hour” for resuscitation even after a traumatic brain injury.

Objective: This study aims to explore the outcome with iv ketamine treatment in a real-world clinical setting, primarily measured as posttreatment days hospitalised. Methods: The psychiatric medical records of 46 patients having received iv ketamine on a psychiatric treatment indication between 2015 and 2018 were retrospectively examined. Analysis comparing the number and duration of hospital admissions before and after ketamine treatment as well as logistic regression analysis to investigate clinical predictors of effectiveness, were performed. To assess patients' severity of depressed symptoms records were screened for MADRS-S scores. Results: No significant difference between pre- and posttreatment hospital days (p = 0.170), or number of hospitalisations (p = 0.740) were found. The response rate was 31% and remission rate 21%. None of the predictors showed statistical significance in the logistic model. Conclusion: Iv ketamine treatment showed effectiveness in reducing depressive symptoms even with complex patients in a real-world clinical setting. However, this did not translate to a reduction in hospitalisation. Highlighting the multifaceted challenges posed when implementing iv ketamine treatment in clinical practice.

Objective Intensive care unit (ICU) stay for a serious illness has a long-term impact on patients’ physical and psychological well-being, affecting their ability to return to their everyday life. We aimed to investigate whether there are differences in health status between those who return to work and those who do not, and how demographic characteristics and illness severity impact patients’ ability to return to work 12 months after intensive care for COVID-19. Research methodology This was a prospective longitudinal cohort study. The participants were patients who had been in intensive care for COVID-19 and had worked before contracting COVID-19. Data on return to previous occupational status, demographic data, comorbidities, intensive care characteristics, and health status were collected at a 12-month follow-up visit. Setting General ICU at the Uppsala University Hospital in Sweden. Results Seventy-three participants were included in the study. Twelve months after discharge from the ICU, 77 % (n = 56) had returned to work. The participants who were unable to return to work reported more severe health symptoms. The (odds ratio [OR] for not returning to work was high for critical illness OR, 12.05; 95 % confidence interval [CI], 2.07–70.29, p = 0.006) and length of ICU stay (OR, 1.06; 95 % CI, 1.01–1.11, p = 0.01) Conclusion Two-thirds of the participants were able to return to work within 1 year after discharge from the ICU. The primary factors contributing to the failure to work were duration of the acute disease and presence of severe and persistent long-term symptoms. Implications for clinical practice Patients’ health status must be comprehensively assessed and their ability to return to work should be addressed in the rehabilitation process. Therefore, any complications faced by the patients must be identified and treated early to increase the possibility of their successful return to work.

Background: Efficacy of inhaled therapy such as Nitric Oxide (iNO) during mechanical ventilation may depend on airway patency. We hypothesized that airway closure and lung collapse, countered by positive end-expiratory pressure (PEEP), influence iNO efficacy. This could support the role of an adequate PEEP titration for inhalation therapy. The main aim of this study was to assess the effect of iNO with PEEP set above or below the airway opening pressure (AOP) generated by airway closure, on hemodynamics and gas exchange in swine models of acute respiratory distress syndrome. Fourteen pigs randomly underwent either bilateral or asymmetrical two-hit model of lung injury. Airway closure and lung collapse were measured with electrical impedance tomography as well as ventilation/perfusion ratio (V/Q). After AOP detection, the effect of iNO (10ppm) was studied with PEEP set randomly above or below regional AOP. Respiratory mechanics, hemodynamics, and gas-exchange were recorded. Results: All pigs presented airway closure (AOP > 0.5cmH2O) after injury. In bilateral injury, iNO was associated with an improved mean pulmonary pressure from 49 +/- 8 to 42 +/- 7mmHg; (p = 0.003), and ventilation/perfusion matching, caused by a reduction in pixels with low V/Q and shunt from 16%[IQR:13-19] to 9%[IQR:4-12] (p = 0.03) only at PEEP set above AOP. iNO had no effect on hemodynamics or gas exchange for PEEP below AOP (low V/Q 25%[IQR:16-30] to 23%[IQR:14-27]; p = 0.68). In asymmetrical injury, iNO improved pulmonary hemodynamics and ventilation/perfusion matching independently from the PEEP set. iNO was associated with improved oxygenation in all cases. Conclusions: In an animal model of bilateral lung injury, PEEP level relative to AOP markedly influences iNO efficacy on pulmonary hemodynamics and ventilation/perfusion match, independently of oxygenation.

Background: Centralisation of perioperative care for small children to a limited number of specialised paediatric centres has many theoretical advantages, but neither the optimal balance nor the current distribution of paediatric anaesthesia on a national scale are well elucidated. The aim of this study was to describe the distribution, adverse events, and mortality in children undergoing anaesthesia in Sweden. Methods: In this cohort study, data from all paediatric anaesthesia procedures registered in Sweden during the years 2019-22 were extracted from the Swedish Perioperative Register (SPOR). Data were analysed according to hospital level of care and ASA physical status. Results: Data from 81 hospitals were analysed. During the 4-yr period, 214,964 procedures were registered. Most procedures in neonates and infants were managed in paediatric (73%) and other university hospitals (21%). Adverse events occurred in 2.71% of cases and severe adverse events in 0.067%. The all-cause 24-h mortality rate was 6.6:10,000 anaesthetics and the all-cause 30-day mortality was 14.7:10,000 anaesthetics. The 30-day all-cause estimated mortality was highest in paediatric hospitals (95% confidence interval [CI] 30-39) compared with other university hospitals (95% CI 6.1-12), county (95% CI 1.9-4.8), district (95% CI 0.07-2.2), and smaller hospitals (95% CI 0.0-22). Conclusions: Most procedures in neonates and infants were performed in tertiary centres, with county hospitals managing mainly older children, in accordance with national recommendations. Mortality was more common in tertiary centres, reflecting increased comorbidity and centralisation of anaesthesia of neonates and infants.

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.

Background: Acute kidney injury (AKI) is common in critical cases of coronavirus disease 2019 (COVID-19) and associated with worse outcome. Dysregulated neutrophil extracellular trap (NET) formation is one of several suggested pathophysiological mechanisms involved in the development of COVID-19 associated AKI. The corticosteroid dexamethasone was implemented as a standard treatment for severe COVID-19 as of June 2020. A sub-analysis of a prospective observational single center study was performed to evaluate the effect of corticosteroid treatment on AKI development and NET markers in critical cases of COVID-19. Results: Two hundred and ten adult patients admitted to intensive care at a tertiary level hospital due to respiratory failure or shock secondary to SARS-CoV-2-infection between March 13th 2020 and January 14th 2021 were included in the study. Ninety-seven of those did not receive corticosteroids. One hundred and thirteen patients were treated with corticosteroids [dexamethasone (n = 98) or equivalent treatment (n = 15)], but the incidence of AKI was assessed only in patients that received corticosteroids before any registered renal dysfunction (n = 63). Corticosteroids were associated with a lower incidence of AKI (19% vs 55.8%, p < 0.001). Fewer patients demonstrated detectable concentrations of extracellular histones in plasma when treated with corticosteroids (8.7% vs 43.1%; p < 0.001). Extracellular histones and in particular non-proteolyzed histones were observed more frequently with increasing AKI severity (p < 0.001). MPO-DNA was found in lower concentrations in patients that received corticosteroids before established renal dysfunction (p = 0.03) and was found in higher concentrations in patients with AKI stage 3 (p = 0.03). Corticosteroids did not ameliorate established AKI during the first week of treatment. Conclusion: Corticosteroid treatment in severe COVID-19 is associated with a lower incidence of AKI and reduced concentrations of NE

Background: Nitrous oxide (N2O) use in recreational settings has been increasing in Sweden and Europe and consequently, the related injuries are also increasing. We aimed to investigate the incidence, management, and surgical outcomes of frostbite injury (FI) related to N2O use. Material and Method: All patients in a 22-month period from 2021 to 2022 presenting with FI related to N2O abuse from 2 plastic surgery clinics (1 national burn center) were identified. Data regarding patient comorbidity, mechanism of injury, initial management, treatment, and follow-up were investigated. Complications following surgery were categorized into minor (treated in outpatient setting) and major (requiring reoperation) complications. Results: In total, 9 patients were identified; among them, 5 patients provided consent and were included in the study. Direct contact with the gas canister was the most common injury mechanism (n = 4). All but 1 patient contracted full-thickness injuries, and these 4 patients later required surgery. The medial thigh was the most common area of injury. Outpatient clinic visits were common (mean 4.8 visits/patient). Surgical complications were common and all operated patients were diagnosed with minor complications and half of them with major complications (wound dehiscence and scar contracture). Conclusion: Frostbite injuries arising from recreational N2O use are complex and often require surgical intervention that may lead to complications. With the increasing incidence of N2O abuse in Sweden, further research is crucial to address this emerging public health concerns and optimize treatment strategies for these distinctive injuries.

Introduction: Cerebral contusions (CCs) are common traumatic brain injuries known for their propensity to progress. Understanding their mechanical pathogenesis and predictive factors for progression is crucial for optimal management. Research question: To provide an overview of current knowledge on CCs, including pathomechanisms, predictive factors of contusion progression, and management strategies. Material and methods: A literature search was conducted using PubMed, Scopus and ISI web of knowledge focused on articles in English with the words "cerebral contusion" together with the words "traumatic brain injury", "pathomechanism", "progression of contusion", "predictive factors" and "management" alone or in combination. Results: The management of CCs has evolved alongside the advances in neurointensive care, yet there is no consensus. Evidence on the effectiveness of early surgery, importantly, for the group which has the potential to expand, is limited. Some predictive factors for contusion progression have been identified, including age, injury mechanism, coagulopathy and initial contusion volume which could help to guide decision-making. Discussion and conclusion: While various theories exist on pathomechanisms and several predictive factors for progression have been proposed, consensus on optimal management remains elusive. Individualized care guided by the predictive factors is essential. Challenges posed by antithrombotic medications highlight the need for early intervention strategies. Decompressive craniectomy could serve as a potential tool in severe traumatic brain injury management including contusions. Conducting large cohort studies to refine predictive models and harmonizing management approaches would help to improve outcomes of patients with CCs.

Purpose This study explores the association of the American Society of Anesthesiologists (ASA) score with 90-day mortality in complicated mild traumatic brain injury (mTBI) patients, and in trauma patients without a TBI. Methods This retrospective study was conducted using a cohort of trauma patients treated at a level III trauma center in Stockholm, Sweden from January to December 2019. The primary endpoint was 90-day mortality. The population was identified using the Swedish Trauma registry. The Trauma and Injury Severity Score (TRISS) was used to estimate the likelihood of survival. Trauma patients without TBI (NTBI) were used for comparison. Data analysis was conducted using R software, and statistical analysis included univariate and multivariate logistic regression. Results A total of 244 TBI patients and 579 NTBI patients were included, with a 90-day mortality of 8.2% (n = 20) and 5.4% (n = 21), respectively. Deceased patients in both cohorts were generally older, with greater comorbidities and higher injury severity. Complicated mTBI constituted 97.5% of the TBI group. Age and an ASA score of 3 or higher were independently associated with increased mortality risk in the TBI group, with odds ratios of 1.04 (95% 1.00-1.09) and 3.44 (95% CI 1.10-13.41), respectively. Among NTBI patients, only age remained a significant mortality predictor. TRISS demonstrated limited predictive utility across both cohorts, yet a significant discrepancy was observed between the outcome groups within the NTBI cohort. Conclusion This retrospective cohort study highlights a significant association between ASA score and 90-day mortality in elderly patients with complicated mTBI, something that could not be observed in comparative NTBI cohort. These findings suggest the benefit of incorporating ASA score into prognostic models to enhance the accuracy of outcome prediction models in these populations, though further research is warranted.

Burn mass casualty event occurrences are rare but will place significant burdens on any burn unit or healthcare system. Effective disaster preparedness plays a significant role in mitigating the aftermath of a burn mass casualty. The aim of this study was to assess the resource requirements during the initial two weeks of a burn mass casualty event. Eight patients in a burn mass casualty event were simulated using the Emergo Train System®. These simulated patients were matched with real historical patients treated in our burn centre, and their resource requirements were analysed. An average of eight staff is required to care for a patient per day along with almost 75 h of operating time (excluding anaesthesia and turnover time). A substantial quantity of consumables was used in the first two weeks. This study has demonstrated the substantial material consumption and staff requirements in the first two weeks of management in a burn mass casualty event. Such findings will offer valuable insight for disaster preparedness planning and resource management strategies.

Background: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated. Methods: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS). Results: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations. Conclusion: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.

Background: Diabetic kidney disease is a major contributor to end stage renal disease. A change in kidney oxygen homeostasis leading to decreased tissue oxygen tension is an important factor initiating alterations in kidney function in diabetes. However, the mechanism contributing to changed oxygen homeostasis is still unclear. Hyperglycemia-induced production of reactive oxygen species and an altered response to them have previously been demonstrated. In the present study, chronic treatment with DL-sulforaphane to induce nuclear factor erythroid 2-related factor 2 (Nrf2) expression, a master transcriptional regulator binding to antioxidant response elements inducing increased protection against reactive oxygen species, is studied. Methods: Sprague-Dawley rats were made diabetic using streptozotocin and either left untreated or received daily subcutaneous injections of DL-sulforaphane for 4 weeks. Age-matched non-diabetic rats served as controls. After 4 weeks of treatment, rats were anesthetized using thiobutabarbital, and kidney functions were studied in terms of glomerular filtration rate (GFR), renal blood flow (RBF), sodium transport, kidney oxygen consumption, and kidney oxygen tension. Mitochondria was isolated from kidney cortical tissue and investigated using high-resolution respirometry. Results: GFR was increased in diabetics but not RBF resulting in increased filtration fraction in diabetics. DL-sulforaphane treatment did not affect RBF and GFR in controls but decreased the same parameters in diabetics. Increased GFR resulted in increased sodium transport and oxygen consumption, hence decreased efficiency in diabetics compared to controls. Increased oxygen consumption in diabetics resulted in decreased cortical tissue oxygen tension. DL-sulforaphane treatment decreased oxygen consumption in diabetics, whereas transport efficiency was not significantly affected. DL-sulforaphane treatment increased cortical pO(2) in diabetics. Conclusions: DL-sulforaphane

Background: The effects of obesity on pulmonary gas and blood distribution in patients with acute respiratory failure remain unknown. Dual-energy computed tomography (DECT) is a X-ray-based method used to study regional distribution of gas and blood within the lung. We hypothesized that 1) regional gas/blood mismatch can be quantified by DECT; 2) obesity influences the global and regional distribution of pulmonary gas and blood; 3) regardless of ventilation modality (invasive vs. non-invasive ventilation), patients’ body mass index (BMI) has an impact on pulmonary gas/blood mismatch. Methods: This single-centre prospective observational study enrolled 118 hypoxic COVID-19 patients (92 male) in need of respiratory support and intensive care who underwent DECT. The cohort was divided into three groups according to BMI: 1. BMI<25 kg/m2 (non-obese), 2. BMI = 25–40 kg/m2 (overweight to obese), and 3. BMI>40 kg/m2 (morbidly obese). Gravitational analysis of Hounsfield unit distribution of gas and blood was derived from DECT and used to calculate regional gas/blood mismatch. A sensitivity analysis was performed to investigate the influence of the chosen ventilatory modality and BMI on gas/blood mismatch and adjust for other possible confounders (i.e., age and sex). Results: 1) Regional pulmonary distribution of gas and blood and their mismatch were quantified using DECT imaging. 2) The BMI>40 kg/m2 group had less hyperinflation in the non-dependent regions and more lung collapse in the dependent regions compared to the other BMI groups. In morbidly obese patients, gas and blood were more evenly distributed; therefore, the mismatch was lower than in other patients (30% vs. 36%, p < 0.05). 3) An increase in BMI of 5 kg/m2 was associated with a decrease in mismatch of 3.3% (CI: 3.67% to −2.93%, p < 0.05). Neither the ventilatory modality nor age and sex affected the gas/blood mismatch (p > 0.05). Conclusion: 1) In a hypoxic COVID-19 population needing intens

Title in the list of papers of Fartein Velle's thesis: The effects of cerebral pressure autoregulation status and CPP levels on cerebral metabolism – A pilot study in pediatric traumatic brain injury

The primary objective of this thesis was to explore the importance of comorbidity for long-term survival following admission to the intensive care unit (ICU). By use of routinely collected laboratory biomarkers and by utilising a more detailed analysis of the patient’s hospital discharge history, we aim to challenge traditional risk prediction models and measures of comorbidity. We also apply the more comprehensive prediction model to understand how preexisting comorbidities may interact with a critical illness in older ICU patients and compare long-term mortality with the general population. Finally, we aim to understand the importance of comorbidity in relation to socioeconomic status (SES) when the measurement of comorbidity is optimised. The study was performed by linking data from the Swedish Intensive Care Register (SIR), a hospital clinical laboratory database and several national public authority registers. Routinely collected laboratory biomarkers and quantitative comorbidity measures were compared in Cox regression models adjusting for age, sex and baseline comorbidities with Charlson Comorbidity Index (CCI) and the Simplified Acute Physiology Score (SAPS) version 2 or 3. The mortality in older ICU patients was then compared with individuals from the general population with a landmark of one year. Also, associations between socioeconomic factors and mortality were estimated by using Cox regression models adjusting for age, sex, SAPS3 and baseline comorbidity. Routinely collected biomarkers discriminate both short- and long-term mortality in general ICU patients, almost as well as the SAPS II. The more comprehensive comorbidity prediction model provides a separation of risk categories within strata of age, the CCI, and intermediate SAPS3 strata. Older patients admitted to the ICU, and who survive the first year after an ICU admission, return to close to the mortality rate of the general population having similar comorbidity. Low educational level was associ

Electrical impedance tomography (EIT) is an emerging technology for the non-invasive monitoring of regional distribution of ventilation and perfusion, offering real-time and continuous data that can greatly enhance our understanding and management of various respiratory conditions and lung perfusion. Its application may be especially beneficial for critically ill mechanically ventilated patients. Despite its potential, clear evidence of clinical benefits is still lacking, in part due to a lack of standardization and transparent reporting, which is essential for ensuring reproducible research and enhancing the use of EIT for personalized mechanical ventilation. This report is the result of a four-day expert meeting where we aimed to promote the consistent and reliable use of EIT, facilitating its integration into both clinical practice and research, focusing on the adult intensive care patient. We discuss the state-of-the-art regarding EIT acquisition and processing, applications during controlled ventilation and spontaneous breathing, ventilation-perfusion assessment, and novel future directions.

Background Timing of surgical evacuation of mass lesions in traumatic brain injury (TBI) is crucial. However, due to geographical variations, transportation time to the nearest neurosurgical department may be long. To save time, general surgeons at a local hospital may perform the operation, despite more limited experience in neurosurgical techniques. This study aimed to determine whether patient outcomes differed between those who had undergone emergency neurosurgery at local hospitals by general surgeons vs. at university hospitals by neurosurgeons. Methods A nationwide observational study was performed using data from the Swedish Trauma Registry (SweTrau) between 2018 and 2022. A total of 565 TBI patients (local hospitals, n = 21; university hospitals, n = 544) who underwent intracranial hematoma evacuation within 8 h after arrival at the hospital were included. Data on demography, admission variables, traumatic injuries, and outcome (Glasgow Outcome Scale [GOS]) at discharge were evaluated. Favourable vs. unfavourable outcomes were defined as GOS scores of 4–5 vs. 1–3. Results Compared with those treated at university hospitals, patients treated with intracranial hematoma evacuation at local hospitals had lower median Glasgow Coma Scale (GCS) scores (8 vs. 12, p < 0.001), higher rate of acute subdural hematomas (86% vs. 77%, p < 0.001), and lower rate of contusions (14% vs. 53%, p = 0.01). Being operated on at a local hospital was independently associated with higher mortality (p = 0.03) but with a similar rate of favourable outcome (p = 0.74) in multiple logistic regressions after adjustment for demographic and injury-related variables. Conclusions Although a slightly greater proportion of patients who underwent emergency neurosurgery at local hospitals died, there was no difference in the rate of favourable outcome. Thus, in patients with impending brain herniation, when time is of the essence, evacuation of traumatic intracranial bleeding by general sur

Sepsis continues to be a major cause of death and illness globally, posing significant challenges for healthcare professionals. In the pursuit of more accurate and timely monitoring tools, the concept of capnodynamically derived mixed venous oxygen saturation (Capno-SvO2) has emerged as a promising method. Capno-SvO2 provides a non-invasive way to assess and track SvO2 and could serve as an additional tool alongside more invasive methods like the pulmonary artery catheter. This could potentially be of great value in the care of critically ill patients with sepsis, where alternative minimal invasive monitoring methods may vary in reliability. The aim of the current study was to compare capno-SvO2 against values obtained through pulmonary artery blood sample CO-oximetry and continuous fiberoptic SvO2 monitoring, using a well-established porcine experimental sepsis model. Anesthetized pigs were exposed to a standardized endotoxin infusion sepsis protocol, followed by a series of maneuvers typically applied in sepsis care. Simultaneous recordings were done throughout the experiment for all three monitoring methods. Bland-Altman analysis corrected for repeated measurements was used to assess the agreement of absolute values between the paired recording of CO-oximetry and Capno-SvO2 as well as between CO-oximetry and fiberoptic SvO2. The ability of Capno-SvO2 and fiberoptic SvO2 to track changes was assessed by concordance rate. A total of 10 animals and 275 paired datapoints were included in the study. The majority of the animals displayed pronounced hemodynamical instability in response to endotoxin exposure and subsequent treatment interventions. Analysis of all paired data points showed a bias between Capno-SvO2 and CO-oximetry SvO2 of + 1% with 95% limits of agreement of -14% to + 17%. The corresponding numbers for fiberoptic SvO2 and CO-oximetry SvO2 were -4% and -15% to + 8%. The concordance rate as compared to CO-oximetry, were 97% and 93% for Capno-SvO2 and fiber

Background War causes severe suffering and harm to the civilian population. Knowledge about civilian injury patterns constitutes a part of the dimensioned planning and preparedness for medical care and civilian defence in times of war. This systematic review is conducted on request from The Swedish National Board of Health and Welfare and includes civilian injury patterns in modern war. Methods The aim of the study is to describe civilian injury patterns in war 1973–2023. We have conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The protocol has been registered 2023-05-06 in PROSPERO (CRD4202321483). Results The search resulted in 3455 identified articles. 1226 of those were duplicates. 2229 studies were assessed, and 1817 papers were excluded. 412 papers went through full text assessment resulting in 63 remaining papers. Injuries to the extremities constitutes 50%, followed by head injuries (26%) and injuries to the chest (18%). Notably, 23% of the wounded are children. Discussion There is no standardized classification or method to report and describe civilian war injuries and the injury panorama. Variations in how the injuries were reported made synthesis of the results difficult. In the present survey we haven’t investigated mortalities and causes of death. Reliable data from recent wars, such as the ongoing war in Ukraine and Gaza, was missing from the open literature. Conclusions The distribution of injuries seems comparable with data from World War II and the conflict in Korea. There is no standardized simple protocol to report civilian injuries in war. Ideally, a protocol should include even the severity impact of the injuries. Knowledge of civilian injury pattern and estimate of the total number of wounded is important to plan the civilian health care capabilities in war time.

Organization of healthcare strongly differs between European countries and results in country-specific requirements in postgraduate medical training. Within the European Union (EU), the European Board of Anaesthesiology has set recommendations of training for the Specialty of Anaesthesiology including standards for Postgraduate Medical Specialist training including a description for providing service in pediatric anesthesia. However, these standards are advisory and not mandatory. Here we aimed to review the current state and associated challenges of pediatric anesthesia training in Europe. We report an important country-specific variability both in training and regulations of practice of pediatric anesthesia in the EU and in the United Kingdom. The requirements for training in pediatric anesthesia varies between nothing specified (Belgium) or providing anesthesia with direct supervision to a minimum of 50 cases below 5 years of age (Germany) to 3–6 month clinical practice in a specialized pediatric hospital (France). Likewise, the regulations for providing anesthesia to children varies from no regulations at all (Belgium) to age specific requirements and centralization of all children below 4 years of age to specified centers (United Kingdom). Officially recognized pediatric anesthesia fellowship programs are not available in most countries of Europe. It remains unclear if and how country-specific differences in pediatric anesthesia training are associated with clinical outcomes in pediatric perioperative care. There is converging interest and support for the establishment of a European pediatric anesthesia curriculum.

BACKGROUND: Popularity of electrical impedance tomography (EIT) and esophageal pressure (Pes) monitoring in the ICU is increasing, but there is uncertainty regarding their bedside use within a personalized ventilation strategy. We aimed to gather insights about the current experiences and perceived role of these physiological monitoring techniques, and to identify barriers and facilitators/solutions for EIT and Pes implementation. METHODS: Qualitative study involving (1) a survey targeted at ICU clinicians with interest in advanced respiratory monitoring and (2) an expert focus group discussion. The survey was shared via international networks and personal communication. An in-person discussion session on barriers, facilitators/solutions for EIT implementation was organized with an international panel of EIT experts as part of a multi-day EIT meeting. Pes was not discussed in-person, but we found the focus group results relevant to Pes as well. This was confirmed by the survey results and four additional Pes experts that were consulted. RESULTS: We received 138 survey responses, and 26 experts participated in the in-person discussion. Survey participants had diverse background [physicians (54%), respiratory therapists (19%), clinical researchers (15%), and nurses (6%)] with mostly > 10 year ICU experience. 84% of Pes users and 74% of EIT users rated themselves as competent to expert users. Techniques are currently primarily used during controlled ventilation for individualization of PEEP (EIT and Pes), and for monitoring lung mechanics and lung stress (Pes). EIT and Pes are considered relevant techniques to guide ventilation management and is helpful for educating clinicians; however, 57% of EIT users and 37% of Pes users agreed that further validation is needed. Lack of equipment/materials, evidence-based guidelines, clinical protocols, and/or the time-consuming nature of the measurements are main reasons hampering Pes and EIT application. Identified facilitator

OBJECTIVES: To determine if current clinical use of iodine contrast media (ICM) for computerised tomography (CT) increases the risk of acute kidney injury (AKI) and long-term decline in renal function in patients treated in intensive care. METHODS: A retrospective bi-centre cohort study was performed with critically ill subjects undergoing either ICM-enhanced or unenhanced CT. AKI was defined and staged based on the Kidney Disease Improve Global Outcome AKI criteria, using both creatinine and urine output criteria. Follow-up plasma creatinine was recorded three to six months after CT to assess any long-term effects of ICM on renal function. RESULTS: In total, 611 patients were included in the final analysis, median age was 65.0 years (48.0-73.0, quartile 1-quartile 3 (IQR)) and 62.5% were male. Renal replacement therapy was used post-CT in 12.9% and 180-day mortality was 31.2%. Plasma creatinine level on day of CT was 100.0 µmol/L (66.0-166.5, IQR) for non-ICM group and 77.0 µmol/L (59.0-109.0, IQR) for the ICM group. The adjusted odds ratio for developing AKI if the patient received ICM was 1.03 (95% confidence interval 0.64-1.66, p = 0.90). No significant association between ICM and increase in plasma creatinine at long-term follow-up was found, with an adjusted effect size of 2.92 (95% confidence interval - 6.52-12.36, p = 0.543). CONCLUSIONS: The results of this study do not indicate an increased risk of AKI or long-term decline in renal function when ICM is used for enhanced CT in patients treated at intensive care units. CLINICAL RELEVANCE STATEMENT: Patients treated in intensive care units had no increased risk of acute kidney injury or persistent decline in renal function after contrast-enhanced CT. This information underlines the need for a proper risk-reward assessment before denying patients a contrast-enhanced CT. KEY POINTS: • Iodine contrast media is considered a risk factor for the development of acute kidney injury. • Patients receiving iodine contra

Background Urinary tract infections (UTIs) are prevalent among patients carrying indwelling catheters in the intensive care unit (ICU). This study investigates antibiotic use and bacterial colonisation among ICU patients during the third wave of the COVID-19 pandemic, building on our prior discovery of increased Enterococcus colonisation associated with increased cephalosporin use in early COVID-19. Methods Longitudinal urine samples from COVID-19 patients (n = 109) with transurethral catheterisation were analysed for bacterial prevalence, further identified via MALDI-TOF. Microbiological results were combined with clinical data obtained daily, assessed and compared with COVID-19 waves 1 and 2. Results Patients in wave 3 exhibited improved outcomes compared to those in waves 1 and 2, alongside a decrease in antibiotic use. Staphylococcus emerged as the primary bacterium and early colonizer of the urinary tract, potentially due to the absence of antibiotic treatment. Our results imply that length of stay (LOS) correlates solely with enteric pathogens and that antibiotic treatment correlates with colonisation by certain uropathogens, whereas the absence of antimicrobial therapy is associated with rapid colonisation of skin flora. Polymicrobial colonisation was common, predominantly involving Gram-positive bacteria. Conclusion Our findings underscore the complexity of bacteriuria in ICU patients, advocating for targeted surveillance and tailored antibiotic approaches to mitigate UTI risk. Insights into antibiotic use and bacterial colonisation are vital for optimising stewardship practices, combating antimicrobial resistance, and enhancing ICU patient outcomes.

Background: Tranexamic acid (TXA) is increasingly used in the management of haemorrhage during and after delivery and haemorrhage caused by other medical conditions due to its efficacy and safety. However, increasing report of fatal complications from inadvertent intrathecal TXA injection remains a cause of concern. The aim of this case report is to demonstrate clinical presentation and predictors of accidental intrathecal injection of TXA within the structure and processes of care in a health facility. Case Description: A 37-year-old woman, multiparous woman presented with a diagnosis of obstructed labour and, therefore, was scheduled for emergency caesarean section. She was assigned the American Society of Anesthesiology II physical status. Spinal anaesthesia was performed at a sitting position through L4-L5 interspace using a 25-G spinal needle gauge. The anaesthetist injected 3 mL of an aesthetic agent that was prepared earlier as hyperbaric bupivacaine 0.5%. About 2 min after receiving the injection, the patient reported gluteal discomfort and itching and severe back pain. She subsequently developed progressive altered mentation followed by generalized tonic–clonic seizures. General anaesthesia was conducted with propofol (100 mg), pethidine (50 mg) and suxamethonium (100 mg). Episodes of tonic–clonic seizures continued despite treatment with multiple doses of diazepam (10 mg), propofol (100 mg) and phenytoin infusion (1 gm). Postoperatively, the patient was transferred to the intensive care unit with persistent tachycardia (125–138 beats per minute), hypertension (157/105–175/118 mmHg) and oxygen saturation of 90%–95%. She died due to cardiac arrest after 21 h of stay. Conclusion: Medication error such as accidental intrathecal injection of TXA continues to jeopardise the safety of surgery under spinal anaesthesia.

This retrospective study analyzed prognostic factors for neurological improvement and ambulation in 194 adult patients (>= 15 years) with traumatic cervical spinal cord injuries treated at the neurological SCI unit (SCIU) at the Karolinska University Hospital Stockholm, Sweden, between 2010 and 2020. The primary outcome was American spinal injury association impairment scale (AIS) improvement, with secondary focus on ambulation restoration. Results showed 41% experienced AIS improvement, with 51% regaining ambulation over a median follow-up of 3.7 years. Significant AIS improvement (p < 0.001) and reduced bladder/bowel dysfunction (p < 0.001) were noted. Multivariable analysis identified initial AIS C-D (< 0.001), central cord syndrome (p = 0.016), and C0-C3 injury (p = 0.017) as positive AIS improvement predictors, while lower extremity motor score (LEMS) (p < 0.001) and longer ICU stays (p < 0.001) were negative predictors. Patients with initial AIS C-D (p < 0.001) and higher LEMS (p < 0.001) were more likely to regain ambulation. Finally, older age was a negative prognostic factor (p = 0.003). In conclusion, initial injury severity significantly predicted neurological improvement and ambulation. Recovery was observed even in severe cases, emphasizing the importance of tailored rehabilitation for improved outcomes.

Background: Mechanical ventilation is essential for managing acute respiratory distress syndrome (ARDS). The implementation of assisted spontaneous breathing may improve diaphragm function and blood oxygenation. However, the optimal protective settings for assisted spontaneous breathing and positive end-expiratory pressure (PEEP) remain uncertain. During the weaning phase from ventilation, assisted spontaneous breathing is commonly used; however, the relationship between applied PEEP levels, transpulmonary pressure, and atelectasis formation during this process is not well understood. We hypothesised that 1) higher PEEP levels may mitigate injurious lung phenomena and 2) atelectasis formation is linearly correlated with transpulmonary pressure during ventilator weaning. Method: The effects of six different PEEP levels on atelectasis, tidal recruitment–derecruitment (R/D), lung stress and tidal volume distribution were tested in two studies involving experimental ARDS (Studies I and II). Furthermore, the effects of PEEP on inspiratory efforts and the effort-to-drive ratio were analysed retrospectively (Study III). The correlation between atelectasis volume and transpulmonary pressure was assessed during a ramp procedure in patients weaning from mechanical ventilation (Study IV). Results: In experimental ARDS, lung weight affected by atelectasis and tidal R/D decreased significantly with increasing PEEP levels (PEEP 0 vs 15 cmH2O, p < 0.01). Higher PEEP levels shifted the tidal volume distribution dorsally. The oesophageal pressure swing and the effort-to-drive ratio showed a significant association with the applied PEEP level (p < 0.01). Shifting PEEP from 0 to 15 cmH2O resulted in a decrease in the mean (SD) oesophageal pressure swing from -4.2 (3.1) to -1.9 (1.5) cmH2O (p < 0.01). In humans, the end-expiratory volume of atelectasis decreased significantly with reduced positive pressures (p < 0.05) and was linearly correlated with end-expiratory transp

Background: Awake proning in spontaneously breathing patients with hypoxemic acute respiratory failure was applied during the coronavirus disease 2019 (COVID-19) pandemic to improve oxygenation while avoiding tracheal intubation. An updated systematic review and meta-analysis on the topic was published.Methods: The Clinical practice committee (CPC) of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) assessed the clinical practice guideline "Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline" for possible endorsement. The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II tool was used.Results: Four out of six SSAI CPC members completed the appraisal. The individual domain totals were: Scope and Purpose 90%; Stakeholder Involvement 89%; Rigour of Development 74%; Clarity of Presentation 85%; Applicability 75%; Editorial Independence 98%; Overall Assessment 79%.Conclusion: The SSAI CPC endorses the clinical practice guideline "Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline". This guideline serves as a useful decision aid for clinicians caring for critically ill patients with COVID-19-related acute hypoxemic respiratory failure and can be used to provide guidance on use of prone positioning in this group of patients., Funding Agencies|Scandinavian Society of Anaesthesiology and Intensive Care Medicine

When treating patients with orthognathic surgery, there might be a risk of obstructive sleep apnoea (OSA) due to soft tissue changes in the upper airways, especially in patients treated with isolated mandibular setback or mandibular setback in combination with maxillary advancement. In the present study, we assessed respiratory function during sleep with home cardiorespiratory polygraphy in 62 patients who had not been previously been diagnosed with OSA at three times: prior to orthognathic surgery for aesthetic and functional indications, and then 3 months and 1 year after surgery. We evaluated surgical displacement based on measurements in three dimensions using pre- and post-operative computed tomography. There were only minor changes in the respiratory parameters such as the apnoea-hypopnoea index (AHI), the apnoea-hypopnoea index in the supine position (AHIsup), the oxygen saturation index (ODI) and the snore index. There was no significant correlation between surgical displacement and the AHI, AHIsup and ODI. There was a weak but significant correlation between vertical displacement of the anterior mandible and the snore index. Within the limitations of the present study, the risk for iatrogenic obstruction of the upper airways seems to be low in patients without OSA treated with orthognathic surgery., Funding Agencies|FORSS (The Research Council of South-Eastern Sweden) [FORSS-649201]; Futurum [FUTURUM-963632]; Interrater reliability of the CT scans; Futurum, Ryhov County Hospital

Background: A prediction model that estimates mortality at admission to the intensive care unit (ICU) is of potential benefit to both patients and society. Logistic regression models like Simplified Acute Physiology Score 3 (SAPS 3) and APACHE are the traditional ICU mortality prediction models. With the emergence of machine learning (machine learning) and artificial intelligence, new possibilities arise to create prediction models that have the potential to sharpen predictive accuracy and reduce the likelihood of misclassification in the prediction of 30-day mortality. Methods: We used the Swedish Intensive Care Registry (SIR) to identify and include all patients >= 18 years of age admitted to general ICUs in Sweden from 2008 to 2022 with SAPS 3 score registered. Only data collected within 1 h of ICU admission was used. We had 153 candidate predictors including baseline characteristics, previous medical conditions, blood works, physiological parameters, cause of admission, and initial treatment. We stratified the data randomly on the outcome variable 30-day mortality and created a training set (80% of data) and a test set (20% of data). We evaluated several hundred prediction models using multiple ML frameworks including random forest, gradient boosting, neural networks, and logistic regression models. Model performance was evaluated by comparing the receiver operator characteristic area under the curve (AUC-ROC). The best performing model was fine-tuned by optimizing hyperparameters. The model's calibration was evaluated by a calibration belt. Ultimately, we simplified the best performing model with the top 1-20 predictors. Results: We included 296,344 first-time ICU admissions. We found age, Glasgow Coma Scale, creatinine, systolic blood pressure, and pH being the most important predictors. The AUC-ROC was 0.884 in test data using all predictors, specificity 95.2%, sensitivity 47.0%, negative predictive value of 87.9% and positive predictive value of 70.7%, Funding Agencies|Department of Anesthesiology and Intensive Care Medicine, Sahlgrenska University Hospital, Moelndal, Sweden; Swedish Research Council [2019-02019]; Swedish government [ALFGBG-971482]; Wallenberg Centre for Molecular and Translational Medicine

Background In 2017 the Swedish public insurance company Löf published national guidelines for in-hospital trauma team activation (TTA), which are now widely adopted in Sweden. No studies have examined triage accuracy at non-trauma-center hospitals in the Stockholm trauma system since the implementation of the new TTA criteria. Aim To assess trauma triage accuracy at one non-trauma-center hospital in Stockholm. Methods 3528 trauma patients treated at Södersjukhuset during 2019–2022 were acquired from the Swedish Trauma Registry (SweTrau) to calculate TTA triage accuracy. Undertriage was defined in accordance with national guidelines as patients with a New Injury Severity Score > 15 who did not prompt level 1 TTA on arrival to hospital. Results In total there were 849 severely injured patients during the study period, of which 2.2% (n = 19) prompted TTA level 1, corresponding to an undertriage of 98% (n = 830). Of the 849 severely injured patients, 41% (n = 348) prompted TTA level 2 whereas the remaining 57% (n = 482) prompted no TTA on arrival to hospital. There were a total of 3046 patients prompting TTA during the study period, but only 19% (n = 19) of level 1 and 12% (n = 348) of level 2 patients were severely injured, and 45% had a NISS ≤ 3. Conclusion Undertriage of severely injured trauma patients was 98% according to the definition specified by Swedish trauma triage guidelines, higher than reasonably acceptable. There is considerable overtriage with non-severely injured patients prompting TTA. However, the suitability of using NISS > 15 to retrospectively define the need for TTA is debatable as this does not always correlate with the fulfillment of the TTA criteria. Further investigation of adherence to trauma triage guidelines in clinical practice may be of value to improve triage accuracy in organized regional trauma systems., Funding Agencies|Karolinska Institute

Cerebral blood flow (CBF) is carefully monitored in the Neurointensive Care Unit (NICU) to prevent secondary brain insults in patients who have suffered subarachnoid hemorrhage. Including absolute MRI measurements of CBF in the NICU monitoring protocol could add valuable information and potentially improve patient outcomes. This is particularly feasible at Link & ouml;ping University Hospital, which uniquely has an MRI scanner located in the NICU, enabling longitudinal CBF measurements while eliminating medical transportation risks. Arterial spin labeling is a subtraction-based MRI technique that can measure CBF globally in the brain without the use of contrast agents, and thus is suitable for repeated measurements over short time periods. Therefore, this work aims to develop and implement a methodological workflow for the acquisition, analysis, absolute quantification, and visualization of longitudinal arterial spin labeling MRI measurements acquired in the clinical NICU setting. At this initial stage, the workflow was implemented and tested using acquired test-retest data and longitudinal data from two healthy participants. Subsequently, the workflow was tested in clinical practice on an intubated and ventilated patient monitored in the NICU after suffering a subarachnoid hemorrhage. To ensure accurate day-to-day comparisons between the repeated measurements, the selection of processing and analysis methods aimed to obtain CBF maps in absolute units of ml/min/100g. These CBF maps were quantified using both the FMRIB Software Library and an openly available flow territory atlas. The test-retest data showed small variations (4.4 ml/min/100g between sessions), and the longitudinal measurement resulted in low CBF variability over 12 days. Despite the greater complexity of clinical data, the quantification and chosen visualization tools proved helpful in interpreting the results. In conclusion, this workflow including repeated MRI measurements could help detect cha, Funding Agencies|Swedish Foundation for Strategic Research [RMX18-0056]; Swedish Research Council [2020-03131]

Background Patients with severe coronavirus disease 2019 (COVID) pneumonia and acute respiratory distress syndrome (C-ARDS) on invasive mechanical ventilation (IMV) have been found to be prone to having other microbial findings than severe acute respiratory syndrome coronavirus 2 (SARS-2)-CoV-19 in the bronchoalveolar lavage (BAL) fluid at intubation causing a superinfection. These BAL results could guide empirical antibiotic treatment in complex clinical situations. However, there are limited data on the relationship between microbial findings in the initial BAL at intubation and later ventilator-associated pneumonia (VAP) diagnoses. Objective To analyse the incidence of, and microorganisms responsible for, superinfections in C-ARDS patients at the time of first intubation through microbial findings in BAL fluid. To correlate these findings to markers of inflammation in plasma and later VAP development. Design Retrospective single-centre study. Setting One COVID-19 intensive care unit (ICU) at a County Hospital in Sweden during the first year of the pandemic. Patients All patients with C-ARDS who were intubated in the ICU. Results We analysed BAL fluid specimens from 112 patients at intubation, of whom 31 (28%) had superinfections. Blood levels of the C-reactive protein, procalcitonin, neutrophil granulocytes, and lymphocytes were indistinguishable between patients with and without a pulmonary superinfection. Ninety-eight (88%) of the patients were treated with IMV for more than 48 h and of these patients, 37% were diagnosed with VAP. The microorganisms identified in BAL at the time of intubation are normally found at the oral, pharyngeal, and airway sites. Only one patient had an indistinguishable bacterial strain responsible for both superinfection at intubation and in VAP. Conclusions One fourth of the patients with C-ARDS had a pulmonary superinfection in the lungs that was caused by another microorganism identified at intubation. Routine serum inflammatory mar, Funding Agencies|Futurum - Akademin fr Hlsa och Vrd, Region Jnkpings lns

BackgroundMany prehospital emergency patients receive suboptimal treatment for their moderate to severe pain. Various factors may contribute. We aim to systematically review literature pertaining to prehospital emergency adult patients with acute pain and the pain-reducing effects, adverse events (AEs), and safety issues associated with inhaled analgetic agents compared with other prehospital analgesic agents.MethodsAs part of an initiative from the Scandinavian Society of Anaesthesia and Intensive Care Medicine, we conducted a systematic review (PROSPERO CRD42018114399), applying the PRISMA guidelines, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and Cochrane methods, searching the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination, PubMed, and EMBASE databases (updated March 2024). Inclusion criteria were the use of inhaled analgesic agents in adult patients with acute pain in the prehospital emergency care setting. All steps were performed by minimum of two individual researchers. The primary outcome was pain reduction; secondary outcomes were speed of onset, duration of effect, and relevant AEs.ResultsWe included seven studies (56,535 patients in total) that compared inhaled agents (methoxyflurane [MF] and nitrous oxide [N2O]) to other drugs or placebo. Study designs were randomized controlled trial (1; n = 60), randomized non-blinded study (1; n = 343), and randomized open-label study (1; n = 270). The remaining were prospective or retrospective observational studies. The evidence according to GRADE was of low or very low quality. No combined meta-analysis was possible. N2O may reduce pain compared to placebo, but not compared to intravenous (IV) paracetamol, and may be less effective compared to morphine and MF. MF may reduce pain compared to paracetamol, ketoprofen, tramadol, and fentanyl. Both agents may be associated with marked but primarily mild AEs.ConclusionWe found low-quality evidence suggesting that b, Funding Agencies|The Clinical Practice Committee of the Scandinavian Society of Anaestesiology and Intensive Care Medicine; Clinical Practice Committee of the Scandinavian Society of Anaestesiology and Intensive Care Medicine

Aim: Assess the prognostic ability of a non-highly malignant and reactive EEG to predict good outcome after cardiac arrest (CA). Methods: Prospective observational multicentre substudy of the "Targeted Hypothermia versus Targeted Normothermia after Out-of-hospital Cardiac Arrest Trial", also known as the TTM2-trial. Presence or absence of highly malignant EEG patterns and EEG reactivity to external stimuli were prospectively assessed and reported by the trial sites. Highly malignant patterns were defined as burst-suppression or suppression with or without superimposed periodic discharges. Multimodal prognostication was performed 96 h after CA. Good outcome at 6 months was defined as a modified Rankin Scale score of 0-3. Results: 873 comatose patients at 59 sites had an EEG assessment during the hospital stay. Of these, 283 (32%) had good outcome. EEG was recorded at a median of 69 h (IQR 47-91) after CA. Absence of highly malignant EEG patterns was seen in 543 patients of whom 255 (29% of the cohort) had preserved EEG reactivity. A non-highly malignant and reactive EEG had 56% (CI 50-61) sensitivity and 83% (CI 80-86) specificity to predict good outcome. Presence of EEG reactivity contributed (p < 0.001) to the specificity of EEG to predict good outcome compared to only assessing background pattern without taking reactivity into account. Conclusion: Nearly one-third of comatose patients resuscitated after CA had a non-highly malignant and reactive EEG that was associated with a good long-term outcome. Reactivity testing should be routinely performed since preserved EEG reactivity contributed to prognostic performance., Funding Agencies|Swedish Research Council; Swedish Heart-Lung Foundation; Knutsson Foundation, Laerdal Foundation; (Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research, and Regional Research Support in Region Skane); Laerdal Foundation; Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research; Regional Research Support in Region Skane; Swedish National Health Service

BackgroundThis Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research.MethodsThe RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities.ResultsData from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatot

BACKGROUNDLung protective ventilation is considered standard of care in the intensive care unit. However, modifying the ventilator settings can be challenging and is time consuming. Closed loop modes of ventilation are increasingly attractive for use in critically ill patients. With closed loop ventilation, settings that are typically managed by the ICU professionals are under control of the ventilator's algorithms.OBJECTIVESTo describe the effectiveness, safety, efficacy and workload with currently available closed loop ventilation modes.DESIGNSystematic review of randomised clinical trials.DATA SOURCESA comprehensive systematic search in PubMed, Embase and the Cochrane Central register of Controlled Trials search was performed in January 2023.ELIGIBILITY CRITERIARandomised clinical trials that compared closed loop ventilation with conventional ventilation modes and reported on effectiveness, safety, efficacy or workload.RESULTSThe search identified 51 studies that met the inclusion criteria. Closed loop ventilation, when compared with conventional ventilation, demonstrates enhanced management of crucial ventilator variables and parameters essential for lung protection across diverse patient cohorts. Adverse events were seldom reported. Several studies indicate potential improvements in patient outcomes with closed loop ventilation; however, it is worth noting that these studies might have been underpowered to conclusively demonstrate such benefits. Closed loop ventilation resulted in a reduction of various aspects associated with the workload of ICU professionals but there have been no studies that studied workload in sufficient detail.CONCLUSIONSClosed loop ventilation modes are at least as effective in choosing correct ventilator settings as ventilation performed by ICU professionals and have the potential to reduce the workload related to ventilation. Nevertheless, there is a lack of sufficient research to comprehensively assess the overall impact of these mode

For patients with hemophilia A and high-titer inhibitors treated with bypassing agents there are no reliable methods to assess treatment effect. We investigated the utility of global hemostatic methods in assessing treatment with bypassing agents (rFVIIa or activated prothrombin complex [aPCC]). All patients with hemophilia A and inhibitors followed at the Coagulation Unit or the Pediatric Coagulation Unit at Karolinska University Hospital aged 6 years and above were eligible for this noninterventional study. Baseline plasma samples were spiked with bypassing agents in increasing concentrations (aPCC 50 U/kg, 100 U/kg, 150 U/kg, and rFVIIa 90 mu g/kg and 270 mu g/kg) in vitro. For patients treated with factor concentrates or bypassing agents follow-up samples were collected (in vivo tests). The samples were analyzed using overall hemostatic potential (OHP), and calibrated automated thrombogram, Calibrated Automated Thrombogram (CAT). Nine patients with hemophilia A with inhibitors were included. Spiking with rFVIIa normalized the coagulation potential in 6/8 samples, in 3 only with high dose. Only one sample did not improve adequately after spiking with aPCC. The improvement in hemostasis was reliably shown by both CAT and OHP. The baseline potential was, however, more often measurable by OHP compared to CAT. Factor concentrate had been administered to 5 patients normalizing the hemostatic potential in vivo in 2 (without spiking). The hemostatic improvement induced by spiking with rFVIIa or aPCC is shown by OHP and CAT, but the results have to be evaluated in larger cohorts., Funding Agencies|Baxalta US Inc [IIR-SWE-BXLT-001972, IISR-2017-104237]; Arosenius fondand the Karolinska Institute Foundation for Coagulation Research

BACKGROUND: There is variability in the use of sedatives and analgesics in neonatal intensive care units (NICUs). We aimed to investigate the use of analgesics and sedatives and the management of neonatal pain and distress. METHODS: This was a global, prospective, cross-sectional study. A survey was distributed May-November 2022. The primary outcome of this research was to compare results between countries depending on their socio-sanitary level using the sociodemographic index (SDI). We organized results based on geographical location. RESULTS: The survey collected 1304 responses, but we analyzed 924 responses after database cleaning. Responses from 98 different countries were analyzed. More than 60% of NICUs reported having an analgosedation guideline, and one-third of respondents used neonatal pain scales in more than 80% of neonates. We found differences in the management of sedation and analgesia between NICUs on different continents, but especially between countries with different SDIs. Countries with a higher SDI had greater availability of and adherence to analgosedation guidelines, as well as higher rates of analgosedation for painful or distressing procedures. Countries with different SDIs reported differences in analgosedation for neonatal intubation, invasive ventilation, and therapeutic hypothermia, among others. CONCLUSIONS: Socio-economic status of countries impacts on neonatal analgosedation management. IMPACT: There is significant variability in the pain management practices in neonates. There is a lack of knowledge related to how neonatal pain management practices differ between regions. Sociodemographic index is a key factor associated with differences in neonatal pain management practices across global regions.

Purpose: Application of standardised and automated assessments of head computed tomography (CT) for neuroprognostication after out-of-hospital cardiac arrest. Methods: Prospective, international, multicentre, observational study within the Targeted Hypothermia versus Targeted Normothermia after out-of-hospital cardiac arrest (TTM2) trial. Routine CTs from adult unconscious patients obtained > 48 h <= 7 days post-arrest were assessed qualitatively and quantitatively by seven international raters blinded to clinical information using a pre-published protocol. Grey-white-matter ratio (GWR) was calculated from four (GWR-4) and eight (GWR-8) regions of interest manually placed at the basal ganglia level. Additionally, GWR was obtained using an automated atlas-based approach. Prognostic accuracies for prediction of poor functional outcome (modified Rankin Scale 4-6) for the qualitative assessment and for the pre-defined GWR cutoff < 1.10 were calculated. Results: 140 unconscious patients were included; median age was 68 years (interquartile range [IQR] 59-76), 76% were male, and 75% had poor outcome. Standardised qualitative assessment and all GWR models predicted poor outcome with 100% specificity (95% confidence interval [CI] 90-100). Sensitivity in median was 37% for the standardised qualitative assessment, 39% for GWR-8, 30% for GWR-4 and 41% for automated GWR. GWR-8 was superior to GWR-4 regarding prognostic accuracies, intra- and interrater agreement. Overall prognostic accuracy for automated GWR (area under the curve [AUC] 0.84, 95% CI 0.77-0.91) did not significantly differ from manually obtained GWR. Conclusion: Standardised qualitative and quantitative assessments of CT are reliable and feasible methods to predict poor functional outcome after cardiac arrest. Automated GWR has the potential to make CT quantification for neuroprognostication accessible to all centres treating cardiac arrest patients., Funding Agencies|Vetenskapsrdet

Background: The ability of current depth-of-anaesthesia monitors to differentiate subtle changes in the conscious state has not been well characterised. We examine the variability in bispectral index (BIS) scores associated with disconnected conscious and unconscious states as confirmed by a novel serial awakening paradigm. Methods: Seventy adult participants, given propofol or dexmedetomidine, had a cumulative 1381 electroencephalographic (EEG) recordings across two centres. Participants were awakened periodically, and their recent conscious experience interrogated by structured questioning. BIS were reconstructed from EEG using openibis, and the distribution of BIS scores were compared using linear mixed effects modelling. The predictive capacity of BIS across states of consciousness was also examined. Results: Reconstructed BIS scores correlated significantly with blood concentrations of propofol and dexmedetomidine (all P<0.001). However, while the average BIS was different between baseline wakefulness (mean BIS=95.1 [standard deviation=3.5]); connected consciousness with drug present (84.0 [10.9]); disconnected consciousness (70.0 [16.9]); and unconsciousness (68.1 [16.1]), the interquartile range of these states (3.6, 15.1, 23.3 and 26.8, respectively) indicated high degrees of overlap and individual variability. Connected consciousness could be differentiated from either disconnected consciousness or unconsciousness with 86% accuracy (i.e. 14% error rate), and disconnected consciousness differentiated from unconsciousness with 74% accuracy. Conclusions: These results agree with previous studies that BIS scores fail to reliably differentiate between states of consciousness, exacerbated by segregating connected, disconnected, and unconscious states. To develop a method that reliably identifies the conscious state of an individual (not an average), work is needed to establish the causal mechanisms of disconnection and unconsciousness., © 2024 British Journal of AnaesthesiaCorrespondence Address: J.J. Wehrman; Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; email: Jordan.Wehrman@sydney.edu.au; CODEN: BJANAAnalysis was supported by ANZCA (ANZCA 24/009); the Wisconsin data were supported by the Department of Anesthesiology of the University of Wisconsin and US National Institutes of Health (1R01NS117901-01 to RDS); the Finnish data were supported by the Academy of Finland (266467, 266434); Jane and Aatos Erkko Foundation; VSSHP-EVO (13323); Doctoral Programme of Clinical Investigation, University of Turku Graduate School (AS, OK); Emil Aaltonen Foundation (REK, OK); Signe and Ane Gyllenberg

BackgroundLeft ventricular ejection fraction (LVEF) is inconsistently associated with poor outcomes in patients with sepsis. Newer parameters such as LV longitudinal strain (LVLS), mitral annular plane systolic excursion (MAPSE) and LV longitudinal wall fractional shortening (LV-LWFS) may be more sensitive indicators of LV dysfunction, but are sparsely investigated. Our objective was to evaluate the association between five traditional and novel echocardiographic parameters of LV systolic function (LVEF, peak tissue Doppler velocity at the mitral valve (s '), LVLS, MAPSE and LV-LWFS) and outcomes in patients admitted to the Intensive Care Unit (ICU) with septic shock.MethodsA total of 152 patients admitted to the ICU with septic shock from two data repositories were included. Transthoracic echocardiograms were performed within 24 h of ICU admission. The primary outcome was myocardial injury, defined as high-sensitivity troponin T >= 45 ng/L on ICU admission. Secondary outcomes were organ support-free days (OSFD) and 30-day mortality. We also tested for the prognostic value of the systolic function parameters using multivariable analysis.ResultsLVLS, MAPSE and LV-LWFS, but not LVEF and s ', differed between patients with and without myocardial injury. After adjustment for age, pre-existing cardiac disease, Simplified Acute Physiology (SAPS3) score, Sequential Organ Failure Assessment (SOFA) score, plasma creatinine and presence of right ventricular dysfunction, only MAPSE and LV-LWFS were independently associated with myocardial injury. None of the systolic function parameters were associated with OSFD or 30-day mortality.ConclusionsMAPSE and LV-LWFS are independently associated with myocardial injury and outperform LVEF, s ' and LVLS. Whether these parameters are associated with clinical outcomes such as the need for organ support and short-term mortality is still unclear.Trial registration NCT01747187 and NCT04695119.ConclusionsMAPSE and LV-LWFS are independ, Funding Agencies|Region stergtland

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Objectives: To determine whether intrathecal morphine (ITM) analgesia in abdominal surgery for presumed gynecological malignancy was associated with better self-reported sleep quality postoperatively compared with epidural analgesia (EDA), and to evaluate risk factors for bad sleep quality. Methods: A secondary analysis of a randomized open controlled trial, comparing ITM and EDA as postoperative analgesia in 80 women undergoing laparotomy under general anaesthesia in an enhanced recovery after surgery framework. A total of 38 women allocated to ITM and 39 to EDA completed the study. The Swedish Postoperative Symptoms Questionnaire assessed symptoms and sleep quality during the first postoperative week. Multiple logistic regression models evaluated risk factors. The results are presented as adjusted odds ratios with 95% CIs. Results: The sleep quality night-by-night did not differ significantly between the women who had ITM or EDA. Risk factors for bad sleep quality for night 1 were age (0.91; 0.84–0.99), operation time (1.02; 1.00–1.03), and opioid consumption (0.96; 0.91–0.99). For night 2, regular use of hypnotics preoperatively (15.81; 1.52–164.27) and opioid consumption (1.07; 1.00–1.14) were independent risk factors for bad sleep. After the second night, no risk factors were disclosed. Conclusions: ITM and EDA did not appear to affect the sleep quality postoperatively differently in women undergoing laparotomy for presumed gynecological malignancy. Risk factors for self-reported bad sleep quality varied during the first 3 days after surgery. Younger age, longer operation time, and preoperative use of hypnotics were associated with bad sleep quality, whereas the effect of opioid consumption on sleep quality varied depending on the time since surgery. These findings merit further studies. © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada, Cited by: 0Funding: Swedish Society of Medicine [SLS-404711]; Medical Research Council of South-east Sweden [FORSS-8685]; Linkping University; Region OEstergtland [LIO-356191, LIO-441781]