Synergistic effects of rivaroxaban and hypothermia or acidosis on coagulation initiation measured with ROTEM®: a prospective observational study.

BACKGROUND: Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM®. METHODS: Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing. RESULTS: In total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels. CONCLUSIONS: The combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis. TRIAL REGISTRATION: The study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313.

Central venous catheter tip misplacement: A multicentre cohort study of 8556 thoracocervical central venous catheterisations.

BACKGROUND: There is a paucity of data on the incidence of central venous catheter tip misplacements after the implementation of ultrasound guidance during insertion. The aims of the present study were to determine the incidence of tip misplacements and to identify independent variables associated with tip misplacement. METHODS: All jugular and subclavian central venous catheter insertions in patients ≥16 years with a post-procedural chest radiography at four hospitals were included. Each case was reviewed for relevant catheter data and radiologic evaluations of chest radiographies. Tip misplacements were classified as 'any tip misplacement', 'minor tip misplacement' or 'major tip misplacement'. Multivariable logistic regression analyses were used to investigate associations between predefined independent variables and tip misplacements. RESULTS: A total of 8556 central venous catheter insertions in 5587 patients were included. Real-time ultrasound guidance was used in 91% of all insertions. Any tip misplacement occurred (95% confidence interval) in 3.7 (3.3-4.1)% of the catheterisations, and 2.1 (1.8-2.4)% were classified as major tip misplacements. The multivariable logistic regression analyses showed that female patient gender, subclavian vein insertions, number of skin punctures and limited operator experience were associated with a higher risk of major tip misplacement, whereas increasing age and height were associated with a lower risk. CONCLUSIONS: In this large prospective multicentre cohort study, performed in the ultrasound-guided era, we demonstrated the incidence of tip misplacements to be 3.7 (3.3-4.1)%. Right internal jugular vein catheterisation had the lowest incidence of both minor and major tip misplacement.

Adherence to a restrictive red blood cell transfusion strategy in critically ill patients: An observational study.

BACKGROUND: Randomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels. METHODS: In this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables. RESULTS: In total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110-8110) mL versus 3010 (2890-4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0-10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80-100] vs. 80 [72-90] g/L, p < .001 and 89 [82-96] g/L vs. 83 [79-94], p < .001, respectively). Percentage of days without compliance with the prescribed transfusion trigger was higher in the pre-cohort than in the post-cohort (23% vs. 14%, p < .001). Sensitivity analyses, excluding patients with traumatic brain injury, ischemic heart disease and COVID-19 demonstrated similar results. CONCLUSIONS: Implementation of a restrictive transfusion trigger in a critical care setting resulted in lasting decreased RBC transfusion use and costs, decreased prescribed and actual haemoglobin trigger levels and improved adherence to prescribed haemoglobin trigger levels.

Audio podcast and procedural video use in anaesthesiology and intensive care: A nationwide survey of Swedish anaesthetists.

BACKGROUND: Digital modalities which enable asynchronous learning, such as audio podcasts and videos demonstrating procedures, may benefit acquisition and retention of knowledge and clinical skills. The main objective of this nationwide cross-sectional survey study was to evaluate key aspects and factors related to usage of audio podcasts and procedural videos in anaesthesiology and intensive care. METHODS: A 20-item multiple-choice-question online survey was created through a consensus process including pilot testing among residents and consultants. Data were collected over a 3-month period, September-November 2023. RESULTS: The survey was completed by 466 anaesthetists. More than a third reported using procedural videos ≥1 time per week, whereas fewer than one in four participants used audio podcasts at least once per week. Multivariable logistic regression analysis showed that working at a university hospital, male sex, and younger age were independently associated with podcast use ≥1 time per week, with the highest odds ratio (OR) for younger age (<40 years vs. ≥40 years old; OR 5.86 (95% confidence interval 3.55-9.67), p < .001). Younger age was also significantly associated with higher frequency of video use (OR 1.71 (1.13-2.58), p = .011), while working predominantly in intensive care was associated with a lower frequency of video use. Podcasts were often used during commuting (42.3%), household work (30.7%), and exercise (24.9%), indicating a role in multi-tasking. Approximately half of respondents expressed that audio podcast-based learning has a moderate to very large positive impact on acquisition of theoretical knowledge, as well as practical skills. A vast majority, 85.2%, reported that procedural videos have a moderate to very large impact on development of clinical skills. CONCLUSION: Audio podcasts and procedural videos are appreciated tools with potential to supplement more traditional didactic techniques in anaesthesiology and intensive care. Procedural video use is common, with perceived large effects on development of clinical skills. Further data are needed to fully understand learning outcomes, quality of peer-review processes, and potential sex-differences.

Platelet transfusions in adult thrombocytopenic ICU patients: Protocol for a sub-study of the PLOT-ICU cohort.

INTRODUCTION: Platelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia. METHODS: This is a protocol and statistical analysis plan for a post hoc sub-study of 504 thrombocytopenic patients from the 'Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)'. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis-derived versus pooled whole-blood-derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight-based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell- and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow-up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively. CONCLUSIONS: The outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT-ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients.

Platelet transfusions in adult ICU patients with thrombocytopenia: A sub-study of the PLOT-ICU inception cohort study.

BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown. STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 109/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 1011 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 1011 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 109/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.

Operator gender differences in major mechanical complications after central line insertions: a subgroup analysis of a prospective multicentre cohort study.

BACKGROUND: A previous study on mechanical complications after central venous catheterisation demonstrated differences in complication rates between male and female operators. The objective of this subgroup analysis was to further investigate these differences. The hypothesis was that differences in distribution of predefined variables between operator genders could be identified. METHODS: This was a subgroup analysis of a prospective, multicentre, observational cohort study conducted between March 2019 and December 2020 including 8 586 patients ≥ 16 years receiving central venous catheters at four emergency care hospitals. The main outcome measure was major mechanical complications defined as major bleeding, severe cardiac arrhythmia, pneumothorax, arterial catheterisation, and persistent nerve injury. Independent t-test and χ2 test were used to investigate differences in distribution of major mechanical complications and predefined variables between male and female operators. Multivariable logistic regression analysis was used to determine association between operator gender and major mechanical complications. RESULTS: Female operators had a lower rate of major mechanical complications than male operators (0.4% vs 0.8%, P = .02), were less experienced (P < .001), had more patients with invasive positive pressure ventilation (P < .001), more often chose the internal jugular vein (P < .001) and more frequently used ultrasound guidance (P < .001). Male operators more often chose the subclavian vein (P < .001) and inserted more catheters with bore size ≥ 9 Fr (P < .001). Multivariable logistic regression analysis showed that male operator gender was associated with major mechanical complication (OR 2.67 [95% CI: 1.26-5.64]) after correction for other relevant independent variables. CONCLUSIONS: The hypothesis was confirmed as differences in distribution of predefined variables between operator genders were found. Despite being less experienced, female operators had a lower rate of major mechanical complications. Furthermore, male operator gender was independently associated with a higher risk of major mechanical complications. Future studies are needed to further investigate differences in risk behaviour between male and female operators. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03782324. Date of registration: 20/12/2018.

Macro- and microscopic changes in veins with short-term central venous catheters: an observational autopsy study.

BACKGROUND: Centrally inserted central catheters (CICCs) are indispensable in modern healthcare, but unfortunately, come with complications. Catheter-related thrombosis is a well-known complication reported to occur in 5-30% of patients with CICC. There is a paucity of studies that report the incidence of catheter-related thrombosis after the introduction of real-time ultrasound insertion guidance as clinical practice. This study aimed to demonstrate any pathological macro- or microscopic changes in the vein wall associated with CICCs. METHODS: The study was approved by the Swedish Ethical Review Authority and was conducted at a large university hospital. The study included 12 patients with a short-term CICC who were subject to autopsies. Vessels with inserted catheters were macroscopically and microscopically examined. RESULTS: In total, seven female and five male patients with a median age of 70 (interquartile range 63-76) were included. With one exception, all patients received routine thromboprophylaxis throughout the period with CICC. Most inserted CICCs were 9.5 French (54%) and were inserted in the internal jugular vein (92%). The median time with CICC was seven days (interquartile range 1.8-20). At autopsy, thrombi were observed in all cases (100%), macroscopically and microscopically, attached to the distal portion of the CICC and/or the adjacent vessel wall. Inflammatory changes in the vessel walls were seen in all cases, and varying degrees of fibrosis were demonstrated in eight cases (67%). CONCLUSIONS: This autopsy study demonstrated that catheter-related thrombus formation with adjacent inflammatory and fibrotic vessel wall thickening was very common, despite a limited period of catheter use. The consequences of these findings are important, as thrombi may cause pulmonary embolism and possibly lead to catheter-related infections, and since inflammatory and fibrotic vessel wall thickening may evolve into chronic venous stenosis. Furthermore, the findings are a cause of concern, as CICCs are indispensable in modern healthcare and complications may be masked by the general disease that was the indication for CICC insertion.

The precision of ROTEM EXTEM is decreased in hypocoagulable blood: a prospective observational study.

BACKGROUND: The use of viscoelastic tests is becoming increasingly popular. There is a paucity of validation of the reproducibility of varying coagulation states. Therefore, we aimed to study the coefficient of variation (CV) for the ROTEM EXTEM parameters clotting time (CT), clot formation time (CFT), alpha-angle and maximum clot firmness (MCF) in blood with varying degrees of coagulation strength. The hypothesis was that CV increases in states of hypocoagulability. METHODS: Critically ill patients and patients subjected to neurosurgery at a university hospital during three separate periods were included. Each blood sample was tested in eight parallel channels, yielding the CVs for the tested variables. In 25 patients, the blood samples were analysed both at baseline and after dilution with albumin 5%, as well as after being spiked with fibrinogen, simulating weak and strong coagulation. RESULTS: In total, 225 unique blood samples were collected from 91 patients. All samples were analysed in eight parallel ROTEM channels, resulting in 1,800 measurements. In hypocoagulable samples, defined as those with values outside the normal reference range, the CV of CT was higher (median (interquartile range)) (6.3% (5.1-9.5)) than for normocoagulable samples (5.1% (3.6-7.5)), p < 0.001. CFT showed no difference (p = 0.14), while the CV of alpha-angle was higher in hypocoagulable samples (3.6% (2.5-4.6)) than in normocoagulable samples (1.1% (0.8-1.6), p < 0.001. The CV of MCF was higher in hypocoagulable samples (1.8% (1.3-2.6)) than in normocoagulable samples (1.2% (0.9-1.7)), p < 0.001. The CV ranges for the different variables were as follows: CT: 1.2%-37%, CFT: 1.7%-30%, alpha-angle: 0.0%-17% and MCF: 0.0%-8.1%. CONCLUSIONS: CVs for the EXTEM ROTEM parameters CT, alpha-angle, and MCF increased in hypocoagulable blood compared to blood with normal coagulation, confirming the hypothesis for CT, alpha-angle, and MCF but not for CFT. Furthermore, the CVs for CT and CFT were much higher than those for alpha-angle and MCF. The results demonstrate that EXTEM ROTEM results from patients with weak coagulation should be interpreted with the notion of limited precision and that procoagulative treatment, based only on ROTEM EXTEM, should be given with some caution.

A retrospective multicenter cohort study of the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19.

BACKGROUND: Patients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19. METHOD: This retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients' minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations. RESULTS: In total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients' minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism. CONCLUSIONS: Measuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results. TRIAL REGISTRATION: The study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.

Mechanical complications after central venous catheterisation in the ultrasound-guided era: a prospective multicentre cohort study.

BACKGROUND: Limited data are available on the incidence of mechanical complications after ultrasound-guided central venous catheterisation. We aimed to determine the incidence of mechanical complications in hospitals where real-time ultrasound guidance is clinical practice for central venous access and to identify variables associated with mechanical complications. METHODS: All central venous catheter insertions in patients ≥16 yr at four emergency care hospitals in Sweden from March 2, 2019 to December 31, 2020 were eligible for inclusion. Every insertion was monitored for complete documentation and occurrence of mechanical complications within 24 h after catheterisation. Multivariable logistic regression analyses were used to determine associations between predefined variables and mechanical complications. RESULTS: In total, 12 667 catheter insertions in 8586 patients were included. The incidence (95% confidence interval [CI]) of mechanical complications was 7.7% (7.3-8.2%), of which 0.4% (0.3-0.5%) were major complications. The multivariable analyses showed that patient BMI <20 kg m-2 (odds ratio 2.69 [95% CI: 1.17-5.62]), male operator gender (3.33 [1.60-7.38]), limited operator experience (3.11 [1.64-5.77]), and increasing number of skin punctures (2.18 [1.59-2.88]) were associated with major mechanical complication. Subclavian vein catheterisation was associated with pneumothorax (5.91 [2.13-17.26]). CONCLUSIONS: The incidence of major mechanical complications is low in hospitals where real-time ultrasound guidance is the standard of care for central venous access. Several variables independently associated with mechanical complications can be used for risk stratification before catheterisation procedures, which might further reduce complication rates. CLINICAL TRIAL REGISTRATION: NCT03782324.

Biomarkers of Complement and Platelet Activation are not correlated with the One or Twenty-Four Hours Corrected Count Increments in Prophylactically Platelet Transfused Hematological Patients: a Prospective Cohort Study.

Platelet transfusion refractoriness is a serious clinical concern that complicates the management of thrombocytopenic patients. Previous studies have suggested a potential role for both complement and platelet activation based on in vitro analyses of platelet concentrates. In this study, the post-transfusion platelet response, as indicated by the corrected count increment at 1 and 24 h after prophylactic platelet transfusions, respectively, was correlated with the 1 h post-transfusion Δconcentration (1 h post-transfusion - pretransfusion) of complement and platelet activation biomarkers. The study was registered as a clinical trial at ClinicalTrials.gov (identifier: NCT02601131) and patients were recruited during inpatient care in the hematological department. Soluble terminal complement complexes, soluble P-selectin and soluble CD40 ligand were analyzed. Confirmed alloimmunized patients were excluded. Included subjects were either given platelet transfusions (n = 43) and categorized into four clinical study groups or included in a non-transfused control group (n = 10). In total, 54 transfusions were included. No transfusion-mediated complement activation was observed. The transfusions were associated with a significant increase in the concentration of soluble P-selectin (p < .001), primarily corresponding to the passive infusion of soluble P-selectin-containing plasma residuals. The Δconcentration of soluble P-selectin was, however, not significantly correlated with the corrected count increments. Thus, significant correlations between biomarkers of complement and platelet activation and the post-transfusion platelet response could not be demonstrated in this study.

Central venous catheter-related complications in hematologic patients: An observational study.

BACKGROUND: The frequency of central venous catheter (CVC)-related complications in hematologic patients has previously been studied but some uncertainty remains. Therefore, this observational cohort study was designed primarily to investigate mechanical and infectious complications related to CVC insertion in hematologic patients and secondarily to identify factors associated with these complications. METHODS: Documented data on CVC insertions in all adult hematologic patients who received a CVC from 2013 to 2019 at a University Hospital in Sweden were retrospectively collected. RESULTS: A total of 589 CVC insertions in 387 patients were included. The prevalence of moderate and severe mechanical complications, predominantly comprising grades 2-4 bleeding, was 11%. Preprocedural coagulopathy, number of needle passes, and arterial puncture were all independently associated with grades 2-4 bleeding. The incidence of suspected catheter-related infections (sCRI) was 3.7/1000 catheter days. Higher body mass index and male gender were independently associated with sCRI. CONCLUSIONS: Patients with hematologic malignancies have a high risk of both grades 2-4 bleeding and sCRI after CVC insertion. This underlines the importance of optimizing the conditions at the insertion and also of daily inspections, evaluation of future needs, and extra precautions to avoid sCRI in these susceptible patients.

Platelet transfusions and thrombocytopenia in intensive care units: Protocol for an international inception cohort study (PLOT-ICU).

INTRODUCTION: Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. METHODS: We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 × 109 /L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. CONCLUSION: The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.

ABO and RhD blood group are not associated with mortality and morbidity in critically ill patients; a multicentre observational study of 29 512 patients.

BACKGROUND: The ABO and RhD blood group represent antigens on the surface of erythrocytes. The ABO blood group antigens are also present on multiple other cells. Interestingly, previous studies have demonstrated associations between the blood group and many types of disease. The present study aimed to identifying associations between the ABO blood group, the RhD blood group, and morbidity and mortality in a mixed cohort and in six pre-defined subgroups of critically ill patients. METHODS: Adult patients admitted to any of the five intensive care units (ICUs) in the Scania Region, Sweden, between February 2007 and April 2021 were eligible for inclusion. The outcomes were mortality analysed at 28- and 90-days as well as at the end of observation and morbidity measured using days alive and free of (DAF) invasive ventilation (DAF ventilation) and DAF circulatory support, including vasopressors or inotropes (DAF circulation), maximum Sequential Organ Failure Assessment score (SOFAmax) the first 28 days after admission and length of stay. All outcomes were analysed in separate multivariable regression models adjusted for age and sex. In addition, in a sensitivity analysis, five subgroups of patients with the main diagnoses sepsis, septic shock, acute respiratory distress syndrome, cardiac arrest and trauma were analysed using the same separate multivariable regression models. RESULTS: In total, 29,512 unique patients were included in the analyses. There were no significant differences for any of the outcomes between non-O blood groups and blood group O, or between RhD blood groups. In the sensitivity analysis of subgroups, there were no differences in mortality between non-O blood groups and blood group O or between the RhD blood groups. AB was the most common blood group in the COVID-19 cohort. CONCLUSIONS: The ABO and RhD blood group do not influence mortality or morbidity in a general critically ill patient population.

Biofilm formation on three different endotracheal tubes: a prospective clinical trial.

BACKGROUND: Biofilm formation on endotracheal tubes (ETTs) is an early and frequent event in mechanically ventilated patients. The biofilm is believed to act as a reservoir for infecting microorganisms and thereby contribute to development and relapses of ventilator-associated pneumonia (VAP). Once a biofilm has formed on an ETT surface, it is difficult to eradicate. This clinical study aimed to compare biofilm formation on three widely used ETTs with different surface properties and to explore factors potentially predictive of biofilm formation. METHODS: We compared the grade of biofilm formation on ETTs made of uncoated polyvinyl chloride (PVC), silicone-coated PVC, and PVC coated with noble metals after > 24 h of mechanical ventilation in critically ill patients. The comparison was based on scanning electron microscopy of ETT surfaces, biofilm grading, surveillance and biofilm cultures, and occurrence of VAP. RESULTS: High-grade (score ≥ 7) biofilm formation on the ETTs was associated with development of VAP (OR 4.17 [95% CI 1.14-15.3], p = 0.031). Compared to uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation (OR 0.18 [95% CI 0.06-0.59], p = 0.005, and OR 0.34 [95% CI 0.13-0.93], p = 0.036, respectively). No significant difference was observed between silicon-coated ETTs and noble-metal-coated ETTs (OR 0.54 [95% CI 0.17-1.65], p = 0.278). In 60% of the oropharyngeal cultures and 58% of the endotracheal cultures collected at intubation, the same microorganism was found in the ETT biofilm at extubation. In patients who developed VAP, the causative microbe remained in the biofilm in 56% of cases, despite appropriate antibiotic therapy. High-grade biofilm formation on ETTs was not predicted by either colonization with common VAP pathogens in surveillance cultures or duration of invasive ventilation. CONCLUSION: High-grade biofilm formation on ETTs was associated with development of VAP. Compared to the uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation. Further research on methods to prevent, monitor, and manage biofilm occurrence is needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02284438 . Retrospectively registered on 21 October 2014.

Morbidity and mortality in critically ill patients with invasive group A streptococcus infection: an observational study.

BACKGROUND: Group A streptococci (GAS) are known to cause serious invasive infections, but little is known about outcomes when patients with these infections are admitted to intensive care. We wanted to describe critically ill patients with severe sepsis or septic shock due to invasive GAS (iGAS) and compare them with other patients with severe sepsis or septic shock. METHODS: Adult patients admitted to a general intensive care unit (ICU) in Sweden (2007-2019) were screened for severe sepsis or septic shock according to Sepsis 2 definition. Individuals with iGAS infection were identified. The outcome variables were mortality, days alive and free of vasopressors and invasive mechanical ventilation, maximum acute kidney injury score for creatinine, use of continuous renal replacement therapy and maximum Sequential Organ Failure Assessment score during the ICU stay. Age, Simplified Acute Physiology Score (SAPS 3) and iGAS were used as independent, explanatory variables in regression analysis. Cox regression was used for survival analyses. RESULTS: iGAS was identified in 53 of 1021 (5.2%) patients. Patients with iGAS presented a lower median SAPS 3 score (62 [56-72]) vs 71 [61-81]), p <  0.001), had a higher frequency of cardiovascular cause of admission to the ICU (38 [72%] vs 145 [15%], p <  0.001) and had a higher median creatinine score (173 [100-311] vs 133 [86-208] µmol/L, p <  0.019). Of the GAS isolates, 50% were serotyped emm1/T1 and this group showed signs of more pronounced circulatory and renal failure than patients with non-emm1/T1 (p = 0.036 and p = 0.007, respectively). After correction for severity of illness (SAPS 3) and age, iGAS infection was associated with lower mortality risk (95% confidence interval (CI) of hazard ratio (HR) 0.204-0.746, p <  0.001). Morbidity analyses demonstrated that iGAS patients were more likely to develop renal failure. CONCLUSION: Critically ill patients with iGAS infection had a lower mortality risk but a higher degree of renal failure compared to similarly ill sepsis patients. emm1/T1 was found to be the most dominant serotype, and patients with emm1/T1 demonstrated more circulatory and renal failure than patients with other serotypes of iGAS.

Coagulation tests on admission correlate with mortality and morbidity in general ICU patients: An observational study.

BACKGROUND: It is well known that low platelet count on admission to intensive care units (ICU) is associated with increased mortality. However, it is unknown whether prothrombin time (PT-INR) and activated partial thromboplastin time (APTT) on admission correlate with mortality and organ failure. Therefore, the aim of this study was to investigate whether PT-INR and APTT at admission can predict outcome in the critically ill patient after adjusting for severity of illness measured with Simplified Acute Physiology Score 3 (SAPS 3). MATERIALS AND METHODS: Data were retrospectively collected. APTT and PT-INR taken on admission and SAPS 3 score were independent variables in all regression analyses. Survival analysis was done with Cox regression. Organ failure was reported as days alive and free (DAF) of vasopressors and invasive ventilation, need of continuous renal replacement therapy (CRRT) and Acute Kidney Injury Network creatinine score (AKIN-crea). RESULTS: A total of 3585 ICU patients were included. Prolonged APTT correlated with mortality with 95% confidence interval (CI) of hazard ratio 1.001-1.010. Prolonged APTT also correlated with DAF vasopressor, CRRT and AKIN-crea with 95% CI of odds ratio (OR) 1.009-1.034, 1.016-1.037 and 1.009-1.028, respectively. Increased PT-INR correlated with DAF vasopressor and DAF ventilator with 95% CI of OR 1.112-2.014 and 1.135-1.847, respectively. CONCLUSIONS: Activated partial thromboplastin time prolongation was associated with mortality and all morbidity outcomes except the DAF ventilator. PT-INR increase at admission was associated with DAF vasopressor and DAF ventilator. APTT and PT-INR at admission correlate with morbidity, which is not accounted for in the SAPS 3 model.

Catheter-related infections: A Scandinavian observational study on the impact of a simple hygiene insertion bundle.

BACKGROUND: Catheter-related infections (CRIs) and catheter-related bloodstream infections (CRBSIs) are among the most frequent hospital acquired infections. CRI/CRBSI studies in Scandinavian cohorts are scarce. The primary aim of this study was to investigate the CRI/CRBSI incidence and the association between potential risk factors, including the introduction of a simple hygiene insertion bundle and CRIs at a large university hospital in Sweden. METHODS: We retrospectively included all patients aged 12 and above who received a central venous catheter (CVC) or a central dialysis catheter during a 2-year period, 1 year before and 1 year after the implementation of a simple hygiene insertion bundle. Microbiological data, including catheter tip cultures and blood cultures, were merged with CVC insertion data. RESULTS: A total of 1722 catheter insertions in 1428 patients were included. CRI and CRBSI incidence were 1.86/1000 and 0.62/1000 catheter days, respectively. In a multivariable regression model, the implementation of a simple hygiene insertion bundle was the independent factor most strongly associated with significantly lower CRI-incidence (95% confidence interval [CI] of odds ratio [OR] 0.23-0.92, P = .029). Choosing multiple lumen catheters was associated with increasing CRI-incidence (95% CI of OR 1.11-2.39, P = .013). CONCLUSION: The incidence of catheter-related infections and catheter-related bloodstream infections in this Scandinavian cohort was low. The implementation of a simple hygiene insertion bundle seems to be an effective intervention for reducing catheter-related infections. The use of multiple-lumen catheters is associated with increased risk of catheter-related infections.