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Abstract Aims This study aimed to assess the use of high‐sensitivity troponin T (hsTNT) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in screening for cardiac dysfunction [left ventricular (LV) systolic or diastolic dysfunction or right ventricular (RV) dysfunction] in mixed intensive care unit (ICU) patients and establish whether these biomarkers are independently associated with an increased risk of death. Methods We performed a secondary analysis of a single‐centre prospective observational study in which consecutive ICU patients were examined with transthoracic echocardiography (TTE) and cardiac biomarkers. Patients with systolic or diastolic LV dysfunction, RV dysfunction or a combination of these were compared with patients with normal cardiac function. Sensitivity and specificity for different cut‐off levels were calculated using receiver operating characteristic curves. Regression models were used to evaluate the associations between cardiac biomarkers, sepsis, renal failure and mortality. Results A total of 276 patients were included. Most of the patients had cardiac dysfunction on TTE (64%). Combined cardiac dysfunction was most prevalent (71 patients, 26%), followed by isolated diastolic LV dysfunction (40 patients, 15%). Levels of hsTNT and NT‐proBNP were higher in all types of cardiac dysfunction versus patients with normal cardiac function. The area under the curve (AUC) for hsTNT to detect any cardiac dysfunction was 0.75. An optimal cut‐off at 30.5 ng/L rendered a positive predictive value (PPV) of 80% and a negative predictive value (NPV) of 58%. The AUC for NT‐proBNP to detect any cardiac dysfunction was 0.788. Using an optimal cut‐off at 1145 ng/L rendered a PPV of 86% and an NPV of 58%. Using a clinically relevant 90% sensitivity for detecting cardiac dysfunction put the cut‐offs at 14.1 ng/L for hsTNT and 247 ng/L for NT‐proBNP, resulting in a specificity of 48% and 46%, respectively. Levels of NT‐proBNP were associated with sepsis and renal failure (P

Abstract Intensive care unit-acquired infections are complicating events in critically ill patients. In this study we analyzed the incidence, microbiological patterns, and outcome in patients with COVID-19 versus influenza in the intensive care unit (ICU). We included all adult patients treated with invasive mechanical ventilation due to (1) COVID-19 between January 2020 and March 2022, and (2) influenza between January 2015 and May 2023 at Sahlgrenska University Hospital, Sweden. Of the 480 participants included in the final analysis, 436 had COVID-19. The incidence rates of ICU-acquired infections were 31.6/1000 and 9.9/1000 ICU-days in the COVID-19 and influenza cohorts, respectively. Ventilator-associated lower respiratory tract infections were most common in both groups. In patients with COVID-19, corticosteroid treatment was associated with an increased risk of ICU-acquired infections and with higher 90-day mortality in case of infection. Furthermore, ICU-acquired infection was associated with a prolonged time in the ICU, with more difficult-to-treat gram-negative infections in late versus early ventilator-associated lower respiratory tract infections. Further research is needed to understand how the association between corticosteroid treatment and incidence and outcome of ICU-acquired infections varies across different patient categories.

Abstract Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.

Abstract Background Intensive care unit-to-unit transfer due to temporary shortage of beds is increasing in Sweden. Transportation induces practical hazards, and the change of health care provider may prolong the length of stay in intensive care. We previously showed that the risk of death at 90 days did not differ between patients transferred due to a shortage of beds and non-transferred patients with a similar burden of illness in a tertiary intensive care unit. The aim of this study was to widen the analysis to a nation-wide cohort of critically ill patients transferred to another intensive care unit in Sweden due to shortage of intensive care beds. Methods Retrospective comparison between capacity transferred and non-transferred patients, based on data from the Swedish Intensive Care Registry during a 5-year period before the COVID-19 pandemic. Patients with insufficient data entries or a recurring capacity transfer within 90 days were excluded. To assess the association between capacity transfer and death as well as intensive care stay within 90 days after ICU admission, logistic regression models with step-wise adjustment for SAPS3 score, primary ICD-10 ICU diagnosis and the number of days in the intensive care unit before transfer were applied. Results From 161,140 eligible intensive care admissions, 2912 capacity transfers were compared to 135,641 discharges or deaths in the intensive care unit. Ninety days after ICU admission, 28% of transferred and 21% of non-transferred patients were deceased. In the fully adjusted model, capacity transfer was associated with a lower risk of death within 90 days than no transfer; OR (95% CI) 0.71 (0.65–0.69) and the number of days spent in intensive care was longer: 12.4 [95% CI 12.2–12.5] vs 3.3 [3.3–3.3]. Conclusions Intensive care unit-to-unit transfer due to shortage of bed capacity as compared to no transfer during a 5-year period preceding the COVID-19 pandemic in Sweden was associated with lower risk of death within 90 days but with longer stay in intensive care.

Introduction Administration of large volumes of fluids is associated with poor outcome in septic shock. Recent data suggest that non-resuscitation fluids are the major source of fluids in the intensive care unit (ICU) patients suffering from septic shock. The present trial is designed to test the hypothesis that a protocol targeting this source of fluids can reduce fluid administration compared with usual care.Methods and analysis The design will be a multicentre, randomised, feasibility trial. Adult patients admitted to ICUs with septic shock will be randomised within 12 hours of admission to receive non-resuscitation fluids either according to a restrictive protocol or to receive usual care. The healthcare providers involved in the care of participants will not be blinded. The participants, outcome assessors at the 6-month follow-up and statisticians will be blinded. Primary outcome will be litres of fluids administered within 3 days of randomisation. Secondary outcomes will be proportion of randomised participants with outcome data on all-cause mortality; days alive and free of mechanical ventilation within 90 days of inclusion; any acute kidney injury and ischaemic events in the ICU (cerebral, cardiac, intestinal or limb ischaemia); proportion of surviving randomised patients who were assessed by European Quality of Life 5-Dimensions 5-Level questionnaire and Montreal Cognitive Assessment; proportion of all eligible patients who were randomised and proportion of participants experiencing at least one protocol violation.Ethics and dissemination Ethics approval has been obtained in Sweden. Results of the primary and secondary outcomes will be submitted for publication in a peer-reviewed journal.Trial registration number NCT05249088.

Abstract Aims Left ventricular (LV) dysfunction can be triggered by non‐cardiac disease, such as sepsis, hypoxia, major haemorrhage, or severe stress (Takotsubo syndrome), but its clinical importance is not established. In this study, we evaluate the incidence and impact on mortality of LV dysfunction associated with critical illness. Methods and results In this single‐centre, observational study, consecutive patients underwent an echocardiographic examination within 24 h of intensive care unit (ICU) admission. LV systolic dysfunction was defined as an ejection fraction (EF)

Abstract Aims Takotsubo syndrome (TTS) is an acute potentially reversible cardiac syndrome characterized by variable regional myocardial akinesia that cannot be attributed to a culprit coronary artery occlusion. TTS is an important differential diagnosis of acute heart failure where brain natriuretic peptides are elevated. Sacubitril/valsartan is a novel and effective pharmacological agent for the treatment of patients with heart failure. Our aim was to explore whether treatment with sacubitril/valsartan could prevent isoprenaline‐induced takotsubo‐like phenotype in rats. Methods and results A total number of 186 Sprague–Dawley male rats were randomized to receive pretreatment with water (CONTROL, n = 62), valsartan (VAL, n = 62), or sacubitril/valsartan (SAC/VAL, n = 62) before receiving isoprenaline for induction of TTS. We recorded heart rate and blood pressure invasively. Cardiac morphology and function were evaluated by high‐resolution echocardiography 90 min after the administration of isoprenaline. We documented the survival rate at the time of echocardiography. Compared with the CONTROL group, the SAC/VAL group had less pronounced TTS‐like cardiac dysfunction and lower mortality rate, while the VAL group did not differ. Heart rate and blood pressure were not significantly different between the groups. Analysis of cardiac lipids was performed with mass spectrometry. The VAL and SAC/VAL groups had significantly higher levels of lysophosphatidylcholine (LPC), in particular LPC 18:1 and LPC 16:0. Conclusions Pretreatment with sacubitril/valsartan but not with valsartan reduces mortality and attenuates isoprenaline‐induced apical akinesia in the TTS‐like model in rats. Sacubitril/valsartan could be a potential treatment option in patients with TTS in humans.

Abstract Background Patients in the intensive care unit (ICU) are increasingly being transferred between ICUs due to a shortage of ICU beds, although this practice is potentially harmful. However, in tertiary units, the transfer of patients who are not in need of highly specialized care is often necessary. The aim of this study was to assess the association between a 90-day mortality and inter-hospital transfer due to a shortage of ICU beds in a tertiary centre. Methods Data were retrieved from the local ICU database from December 2011 to September 2019. The primary analysis was a risk-adjusted logistic regression model. Secondary analyses comprised case/control (transfer/non-transfer) matching. Results A total of 573 patients were transferred due to a shortage of ICU beds, and 8106 patients were not transferred. Crude 90-day mortality was higher in patients transferred due to a shortage of beds (189 patients (33%) vs 2188 patients (27%), p = 0.002). In the primary, risk-adjusted analysis, the risk of death at 90 days was similar between the groups (odds ratio 0.923, 95% confidence interval 0.75–1.14, p = 0.461). In the secondary analyses, a 90-day mortality was similar in transferred and non-transferred patients matched according to SAPS 3-score, age, days in the ICU and ICU diagnosis (p = 0.407); SOFA score on the day of discharge, ICU diagnosis and age (p = 0.634); or in a propensity score model (p = 0.229). Conclusion Mortality at 90 days in critically ill patients treated in a tertiary centre was not affected by transfer to another intensive care units due to a shortage of beds. We found this conclusion to be valid under the assumption that patients are carefully selected and that the transports are safely performed.

Abstract Aims Takotsubo syndrome (TS) is an acute cardiac syndrome characterized by regional myocardial akinesia that cannot be attributed to a culprit lesion in coronary arteries. Cardiac overstimulation by catecholamines in the setting of stress is implicated in the pathogenesis of TS. While catecholamine‐induced alterations in cardiac contractility have been studied as part of the causal pathway in TS, the importance of catecholamine‐mediated tachycardia has not been studied. Our aim was to explore whether the reduction in heart rate, either by pharmacological suppression of the sinoatrial node with ivabradine or by surgical induction of third‐degree atrioventricular block, prevents isoprenaline‐induced TS‐like akinesia in an experimental animal model. Methods and results We used 142 female Sprague–Dawley rats in two separate protocols. The TS‐like phenotype was induced by an intraperitoneal bolus dose of isoprenaline (ISO) 50 mg/kg. In the first protocol, we randomized 54 rats to ivabradine 10 min before ISO (IVAB1), ivabradine 10 min after ISO (IVAB2), or saline 10 min before ISO (CONTROL). In the second protocol, we randomized 88 rats to surgically induced complete heart block (CHB) or sham operation (CTRL) 10 min before the administration of ISO. All drugs were administered intraperitoneally. We recorded heart rate and blood pressure invasively in the right carotid artery. Cardiac morphology and function were evaluated by high‐resolution echocardiography (VisualSonics 770 VEVO, Toronto, Ontario, Canada) 90 min after ISO injection. IVAB1 and IVAB2 rats had significantly lower heart rate and less pronounced TS‐like cardiac dysfunction than CONTROL. CHB rats had a lower (54%) heart rate, and no animal developed left ventricular akinesia. In the first protocol, the CONTROL group had a median degree of akinesia of 10.2 [inter‐quartile range (IQR) 0.0–18.6]. The IVAB1 group showed a median of akinesia of 0% (IQR 0.0–0.0, P

Introduction Pre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women’s and their partners’ experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia.The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care.Methods and analysis This is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women’s and partner’s experiences are distributed at follow-up.Ethics and dissemination By creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women’s personal identification number and pseudonymised after identification in the biobank before analysis.This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309).Results from the study will be published in international peer-reviewed journals.Trial registration number ISRCTN13060768

BackgroundCerebral injury is a common cause of maternal mortality due to preeclampsia and is challenging to predict and diagnose. In addition, there are associations between previous preeclampsia and stroke, dementia and epilepsy later in life. The cerebral biomarkers S100B, neuron specific enolase, (NSE), tau protein and neurofilament light chain (NfL) have proven useful as predictors and diagnostic tools in other neurological disorders. This case-control study sought to determine whether cerebral biomarkers were increased in cerebrospinal fluid (CSF) as a marker of cerebral origin and potential cerebral injury in preeclampsia and if concentrations in CSF correlated to concentrations in plasma.MethodsCSF and blood at delivery from 15 women with preeclampsia and 15 women with normal pregnancies were analysed for the cerebral biomarkers S100B, NSE, tau protein and NfL by Simoa and ELISA based methods. MRI brain was performed after delivery and for women with preeclampsia also at six months postpartum.ResultsWomen with preeclampsia demonstrated increased CSF- and plasma concentrations of NfL and these concentrations correlated to each other. CSF concentrations of NSE and tau were decreased in preeclampsia and there were no differences in plasma concentrations of NSE and tau between groups. For S100B, serum concentrations in preeclampsia were increased but there was no difference in CSF concentrations of S100B between women with preeclampsia and normal pregnancy.ConclusionNfL emerges as a promising circulating cerebral biomarker in preeclampsia and increased CSF concentrations point to a neuroaxonal injury in preeclampsia, even in the absence of clinically evident neurological complications.