Association between left ventricular systolic function parameters and myocardial injury, organ failure and mortality in patients with septic shock.

BACKGROUND: Left 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. METHODS: A 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. RESULTS: LVLS, 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. CONCLUSIONS: MAPSE 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.

Influenza-associated invasive aspergillosis in patients admitted to the intensive care unit in Sweden: a prospective multicentre cohort study.

BACKGROUND: The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden. METHODS: The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and ß-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions. RESULTS: The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, ß-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% - 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01). CONCLUSIONS: The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04172610, registered November 21, 2019.

New-onset atrial fibrillation in critically ill adult patients-an SSAI clinical practice guideline.

BACKGROUND: Acute or new-onset atrial fibrillation (NOAF) is the most common cardiac arrhythmia in critically ill adult patients, and observational data suggests that NOAF is associated to adverse outcomes. METHODS: We prepared this guideline according to the Grading of Recommendations Assessment, Development and Evaluation methodology. We posed the following clinical questions: (1) what is the better first-line pharmacological agent for the treatment of NOAF in critically ill adult patients?, (2) should we use direct current (DC) cardioversion in critically ill adult patients with NOAF and hemodynamic instability caused by atrial fibrillation?, (3) should we use anticoagulant therapy in critically ill adult patients with NOAF?, and (4) should critically ill adult patients with NOAF receive follow-up after discharge from hospital? We assessed patient-important outcomes, including mortality, thromboembolic events, and adverse events. Patients and relatives were part of the guideline panel. RESULTS: The quantity and quality of evidence on the management of NOAF in critically ill adults was very limited, and we did not identify any relevant direct or indirect evidence from randomized clinical trials for the prespecified PICO questions. We were able to propose one weak recommendation against routine use of therapeutic dose anticoagulant therapy, and one best practice statement for routine follow-up by a cardiologist after hospital discharge. We were not able to propose any recommendations on the better first-line pharmacological agent or whether to use DC cardioversion in critically ill patients with hemodynamic instability induced by NOAF. An electronic version of this guideline in layered and interactive format is available in MAGIC: https://app.magicapp.org/#/guideline/7197. CONCLUSIONS: The body of evidence on the management of NOAF in critically ill adults is very limited and not informed by direct evidence from randomized clinical trials. Practice variation appears considerable.

The Clinical Frailty Scale for mortality prediction of old acutely admitted intensive care patients: a meta-analysis of individual patient-level data.

BACKGROUND: This large-scale analysis pools individual data about the Clinical Frailty Scale (CFS) to predict outcome in the intensive care unit (ICU). METHODS: A systematic search identified all clinical trials that used the CFS in the ICU (PubMed searched until 24th June 2020). All patients who were electively admitted were excluded. The primary outcome was ICU mortality. Regression models were estimated on the complete data set, and for missing data, multiple imputations were utilised. Cox models were adjusted for age, sex, and illness acuity score (SOFA, SAPS II or APACHE II). RESULTS: 12 studies from 30 countries with anonymised individualised patient data were included (n = 23,989 patients). In the univariate analysis for all patients, being frail (CFS ≥ 5) was associated with an increased risk of ICU mortality, but not after adjustment. In older patients (≥ 65 years) there was an independent association with ICU mortality both in the complete case analysis (HR 1.34 (95% CI 1.25-1.44), p < 0.0001) and in the multiple imputation analysis (HR 1.35 (95% CI 1.26-1.45), p < 0.0001, adjusted for SOFA). In older patients, being vulnerable (CFS 4) alone did not significantly differ from being frail. After adjustment, a CFS of 4-5, 6, and ≥ 7 was associated with a significantly worse outcome compared to CFS of 1-3. CONCLUSIONS: Being frail is associated with a significantly increased risk for ICU mortality in older patients, while being vulnerable alone did not significantly differ. New Frailty categories might reflect its "continuum" better and predict ICU outcome more accurately. TRIAL REGISTRATION: Open Science Framework (OSF: https://osf.io/8buwk/ ).

Frailty is a stronger predictor of death in younger intensive care patients than in older patients: a prospective observational study.

BACKGROUND: While frailty is a known predictor of adverse outcomes in older patients, its effect in younger populations is unknown. This prospective observational study was conducted in a tertiary-level mixed ICU to assess the impact of frailty on long-term survival in intensive care patients of different ages. METHODS: Data on premorbid frailty (Clinical Frailty Score; CFS), severity of illness (the Simplified Acute Physiology Score, third version; SAPS3), limitations of care and outcome were collected in 817 adult ICU patients. Hazard ratios (HR) for death within 180 days after ICU admission were calculated. Unadjusted and adjusted analyses were used to evaluate the association of frailty with outcome in different age groups. RESULTS: Patients were classified into predefined age groups (18-49 years (n = 241), 50-64 (n = 188), 65-79 (n = 311) and 80 years or older (n = 77)). The proportion of frail (CFS ≥ 5) patients was 41% (n = 333) in the overall population and increased with each age strata (n = 46 (19%) vs. n = 67 (36%) vs. n = 174 (56%) vs. n = 46 (60%), P < 0.05). Frail patients had higher SAPS3, more treatment restrictions and higher ICU mortality. Frailty was associated with an increased risk of 180-day mortality in all age groups (HR 5.7 (95% CI 2.8-11.4), P < 0.05; 8.0 (4.0-16.2), P < 0.05; 4.1 (2.2-6.6), P < 0.05; 2.4 (1.1-5.0), P = 0.02). The effect remained significant after adjustment for SAPS3, comorbidity and limitations of treatment only in patients aged 50-64 (2.1 (1.1-3.1), P < 0.05). CONCLUSIONS: Premorbid frailty is common in ICU patients of all ages and was found in 55% of patients aged under 64 years. Frailty was independently associated with mortality only among middle-aged patients, where the risk of death was increased twofold. Our study supports the use of frailty assessment in identifying younger ICU patients at a higher risk of death.

[Clinical Frailty Scale - a proxy estimate of biological age]. / Clinical frailty scale ­ skörhet är ett sätt att skatta biologisk ålder.

The term frailty denotes a multi-dimensional syndrome characterised by reduced physiological reserves and increased vulnerability. Frailty may be used as a marker of biological age, distinct from chronological age. There are several instruments for frailty assessment. The Clinical Frailty Scale (CFS) is probably the most commonly used in the acute care context. It is a 9-level scale, derived from the accumulated deficit model of frailty, which combines comorbidity, disability, and cognitive impairment. The CFS assessment is fast and easy to implement in daily clinical practice. The CFS is relevant for risk stratification, and may also be used as a screening instrument to identify frail patients suitable for further geriatric evaluation, i.e. a comprehensive geriatric assessment (CGA). By providing information on long-term prognosis, it may improve informed decision-making on an individual basis.

Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index.

BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality. METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE. RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds. CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE. CLINICAL TRIAL REGISTRATION: NCT03436238.

Sustainment of a patient flow intervention in an intensive care unit in a regional hospital in Australia: a mixed-method, 5-year follow-up study.

OBJECTIVE: In 2014, an escalation plan and morning handover meetings were implemented in an intensive care unit (ICU) to reduce access block for post-operative care. In this study, the improvement intervention is revisited 5 years on with the objective to see if the changes are sustained and to understand factors contributing to sustainability. DESIGN: A mixed-method approach was used, with quantitative analysis of ICU administrative data and qualitative analysis of interviews with hospital management and ICU staff. SETTING: ICU with mixed surgical and non-surgical cases in a regional hospital in Australia. PARTICIPANTS: Interview participants: ICU nurses (four), ICU doctors (four) and hospital management (four). MAIN OUTCOME MEASURES: Monthly number of elective surgeries were cancelled due to unavailability of ICU beds. Staff perceptions of the interventions and factors contributed to sustainability. RESULTS: After a decline in elective surgeries being cancelled in the first year after the intervention, there was an increase in cancellations in the following years (χ2=16.38, p=0.003). Lack of knowledge about the intervention and competitive interests in the management of patient flow were believed to be obstacles for sustained effects of the original intervention. So were communication deficiencies that were reported within the ICU and between ICU and other departments. There are discrepancies between how nurses and doctors use the escalation plan and regard the availability of ICU beds. CONCLUSION: Improvement interventions in healthcare that appear initially to be successful are not necessarily sustained over time, as was the case in this study. In healthcare, there is no such thing as a 'fix and forget' solution for interventions. Management commitment to support communication within and between microsystems, and to support healthcare staff understanding of the underlying reasons for intervention, are important implications for change and change management across healthcare systems.

Left ventricular longitudinal wall fractional shortening accurately predicts longitudinal strain in critically ill patients with septic shock.

BACKGROUND: Left ventricular longitudinal strain (LVLS) may be a sensitive indicator of left ventricular (LV) systolic function in patients with sepsis, but is dependent on high image quality and analysis software. Mitral annular plane systolic excursion (MAPSE) and the novel left ventricular longitudinal wall fractional shortening (LV-LWFS) are bedside echocardiographic indicators of LV systolic function that are less dependent on image quality. Both are sparsely investigated in the critically ill population, and may potentially be used as surrogates for LVLS. We assessed if LVLS may be predicted by LV-LWFS and MAPSE in patients with septic shock. We also assessed the repeatability and inter-rater agreement of LVLS, LV-LWFS and MAPSE measurements. RESULTS: 122 TTE studies from 3 echocardiographic data repositories of patients admitted to ICU with septic shock were retrospectively assessed, of which 73 were suitable for LVLS analysis using speckle tracking. The correlations between LVLS vs. LV-LWFS and LVLS vs. MAPSE were 0.89 (p < 0.001) and 0.81 (p < 0.001) with mean squared errors of 5.8% and 9.1%, respectively. Using the generated regression equation, LV-LWFS predicted LVLS with a high degree of accuracy and precision, with bias and limits of agreement of -0.044 ± 4.7% and mean squared prediction error of 5.8%. Interobserver repeatability was good, with high intraclass correlation coefficients (0.96-0.97), small bias and tight limits of agreement (≤ 4.1% for all analyses) between observers for all measurements. CONCLUSIONS: LV-LWFS may be used to estimate LVLS in patients with septic shock. MAPSE also performed well, but was slightly inferior compared to LV-LWFS in estimating LVLS. Feasibility of MAPSE and LV-LWFS was excellent, as was interobserver repeatability.

Causes of late mortality among ICU-treated patients with sepsis.

BACKGROUND: Patients with sepsis may have an increased risk of late mortality, but the causes of late death are unclear. This retrospective matched cohort study aimed to determine the causes of late death (≥1 year) among patients with sepsis compared to patients without sepsis. METHODS: 8760 patients with severe sepsis or septic shock (2001 consensus criteria) registered in the Swedish Intensive Care Registry (2008-2013) were compared with a 1:1 matched (gender, age, SAPS3 probability for death, ICU length of stay) control group consisting of non-septic ICU patients. Causes of death (International Classification of Diseases codes) were obtained from the Swedish Cause of Death Register (2008-2014). RESULTS: During 2008-2014, 903 patients with sepsis died at ≥365 days after their initial septic event, compared to 884 patients in the control group. Median time of follow-up was 313 days (sepsis group, interquartile range 11-838 days) vs 288 days (control group, 9-836 days). The most common causes of death were heart diseases (sepsis: 50.2%, non-septic: 48.6%) and cancer (sepsis: 33.7%, non-septic: 31.7%). Infectious diseases were significantly more common cause of death in the sepsis group (24.3% vs 19.6%, respectively; P < .05). Pneumonia was a common infectious cause of death in both groups, whereas sepsis was more common in the sepsis group. CONCLUSIONS: The most common causes of late death after ICU admission among patients with and without sepsis were heart diseases and cancer. However, patients with sepsis more frequently had infectious diseases as a cause of late death, compared to non-septic patients.

Frailty predicts 30-day mortality in intensive care patients: A prospective prediction study.

BACKGROUND: Frailty is a multidimensional syndrome characterised by a loss of reserve and an increased risk of adverse outcomes. OBJECTIVE: To study the impact of frailty on mortality in unselected intensive care patients, and to compare its discriminatory ability to an established model for outcome prediction in intensive care. DESIGN: A prospective study with a comparison of two prediction models. SETTING: A tertiary mixed ICU, from January 2017 to June 2018. PATIENTS AND MAIN OUTCOME MEASURES: Data on premorbid frailty (clinical frailty scale; CFS), severity of illness (the simplified acute physiology score, third version; SAPS3), therapeutic procedures, limitations of care and outcome were collected in 872 adult ICU patients. A cut-off level of CFS for predicting death within 30 days was identified and unadjusted and adjusted analyses were used to evaluate the association of frailty to outcome. RESULTS: The receiver operating curve, area under the curve of CFS [0.74 (95% confidence interval, 0.69 to 0.79)] did not differ significantly from that of SAPS3 [0.79 (0.75 to 0.83), P = 0.53], whereas combining the two resulted in an improved discriminatory ability [area under the curve = 0.82 (0.79 to 0.86), CFS + SAPS3 vs. SAPS3 alone, P = 0.02]. The correlation of CFS to SAPS3 was moderate (r = 0.4). A cut-off level was identified at CFS at least 5, defining 43% (n=375) of the patients as frail. Frail patients were older with higher SAPS3 and more comorbidities. Treatment in the ICU was more often withheld or withdrawn in frail patients, and mortality was higher. After adjustment for SAPS3, comorbidities, limitations of treatment, age and sex, frailty remained a strong predictor of death within 30 days [hazard ratio 2.12 (95% confidence interval, 1.44 to 3.14), P < 0.001]. CONCLUSION: Premorbid frailty was common in general ICU patients and was an independent predictor of death. Our study suggests that frailty could be a valuable addition in outcome prediction in intensive care.

Endotoxin Removal in Septic Shock with the Alteco LPS Adsorber Was Safe But Showed no Benefit Compared to Placebo in the Double-Blind Randomized Controlled Trial-the Asset Study.

PURPOSE: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco LPS Adsorber for LPS removal in early gram-negative septic shock was feasible and safe. Also, effects on endotoxin level, inflammatory response, and organ function were assessed. METHODS: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate 32 septic shock patients with abdominal or urogenital focus on LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS binding. The study treatment was initiated within 12 h of inclusion and given for 6 h daily on first 2 days. LPS was measured in all patients. RESULTS: The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups. CONCLUSIONS: In a small cohort of patients with presumed gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared with a sham device was seen when using a LPS adsorber in addition to standard care. TRIAL REGISTRATION: Clinicaltrials.gov NCT02335723. Registered: November 28, 2014.

Nonadherence to antibiotic guidelines in patients admitted to ICU with sepsis is associated with increased mortality: A registry-based, retrospective cohort study.

BACKGROUND: Early appropriate antibiotic therapy is an important component of the Surviving Sepsis Guidelines bundles that are associated with decreased in-hospital mortality. National antibiotic guidelines for the treatment of sepsis in Sweden have been available since 2008. Compliance with these guidelines is largely unknown, and whether it translates to improved patient outcome has not been studied. OBJECTIVE: To assess mortality and its relationship to compliance with Swedish antibiotic guidelines. A secondary aim was to assess the effect of timing of antibiotic administration and mortality. DESIGN: A registry-based, retrospective cohort study. Registry data were supplemented by manual extraction of data on antibiotic treatment from patient charts. The association between guideline compliance and mortality was evaluated using multivariable analysis. Three levels of compliance were predefined: full compliance - correct antibiotics and dose; partial compliance - correct antibiotic but wrong dose and/or wrong initial antibiotic but corrected within 24 h and/or wrong combination in a combined regime that is at least one antibiotic not in line with the national antibiotic guideline; no compliance - incorrect antibiotic. SETTING: Two general ICUs in Sweden between 1 January 2011 and 31 December 2015. PATIENTS: Seven hundred and thirteen patients over the age of 18 with severe sepsis or septic shock identified through the Swedish ICU Registry. MAIN OUTCOME MEASURES: The primary outcome was 30-day mortality. RESULTS: Full compliance was observed in 47.0% of patients, partial compliance in 36.0%, and no compliance in 17.0%. Lack of compliance was independently associated with increased risk of 30-day mortality: the adjusted hazard ratio was 1.86 (95% CI 1.34 to 2.58 P < 0.001) for partial compliance and 2.18 (95% CI 1.34 to 3.40 P < 0.001) for no compliance. The time to first antibiotic administration was not associated with mortality. CONCLUSION: Less than half of the patients with severe sepsis and septic shock received antibiotics according to Swedish national guidelines. Full compliance with the guidelines was associated with decreased mortality. The results of this study show that a strict approach to guideline compliance seems to be beneficial: half measures and inadequate doses should be avoided.

No association with cardiac death after sepsis: A nationwide observational cohort study.

BACKGROUND: Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences and implications for patients remain unclear. The aim of this study was to investigate cardiac outcome in sepsis by assessing causes of death up to 2 years after treatment in an Intensive Care Unit (ICU) in a nationwide register-based cohort collected from the Swedish Intensive Care Registry. METHODS: A cohort of 13 669 sepsis and septic shock ICU patients from 2008 to 2014 was collected together with a non-septic control group, matched regarding age, sex and severity of illness (n = 6582), and all without preceding severe cardiac disease. For a large proportion of the severe sepsis and septic shock patients (n = 7087), no matches were found. Information on causes of death up to 2 years after ICU admission was sought in the Swedish National Board of Health and Welfare's Cause of Death Registry. RESULTS: Intensive Care Unit mortality was nearly identical in a matched comparison of sepsis patients to controls (24% in both groups) but higher in more severely ill sepsis patients for whom no matches were found (33% vs 24%, P < 0.001). There was no association of sepsis to cardiac deaths in the first month (OR 1.03, 95%CI 0.87 to 1.20, P = 0.76) nor up to 2 years after ICU admission (OR 1.01, 95%CI 0.82 to 1.25, P = 0.94) in an adjusted between-group comparison. CONCLUSIONS: There was no association with an increased risk of death related to cardiac disease in patients with severe sepsis or septic shock when compared to other ICU patients with similar severity of illness.

Risk prediction of ICU readmission in a mixed surgical and medical population.

BACKGROUND: Readmission to intensive care units (ICU) is accompanied with longer ICU stay as well as higher ICU, in-hospital and 30-day mortality. Different scoring systems have been used in order to predict and reduce readmission rates. METHODS: The purpose of this study was to evaluate the Stability and Workload Index for Transfer (SWIFT) score as a predictor of readmission. Further, we wanted to study steps and measures taken at the ward prior to readmission. RESULTS: This was a retrospective study conducted at the mixed surgical and medical ICU at Linköping University Hospital. One thousand sixty-seven patients >18 years were admitted to the ICU during 2 years and were included in the study. During the study period, 27 patients were readmitted to the ICU. Readmitted patients had a higher SWIFT score than the non-readmitted (16.1 ± 6.8 vs. 13.0 ± 7.5, p = 0.03) at discharge. The total ICU length of stay was longer (7.5 ± 7.5 vs. 2.9 ± 5.1, p = 0.004), and the 30-day mortality was higher (26 vs. 7 %, p < 0.001) for readmitted patients. Fifty-six percent of readmitted patients were assessed by the critical care outreach service (CCOS) at the ward prior to ICU readmission. A SWIFT score of 15 or more was associated with a significantly higher readmission rate (p = 0.03) as well as 30-day mortality (p < 0.001) compared to a score of ≤14. CONCLUSIONS: A SWIFT score of 15 or more is associated with higher readmission rate and 30-day mortality. The SWIFT score could therefore be used for risk prediction for readmission and mortality at ICU discharge.

Strain echocardiography in septic shock - a comparison with systolic and diastolic function parameters, cardiac biomarkers and outcome.

INTRODUCTION: Myocardial dysfunction is a well-known complication in septic shock but its characteristics and frequency remains elusive. Here, we evaluate global longitudinal peak strain (GLPS) of the left ventricle as a diagnostic and prognostic tool in septic shock. METHODS: Fifty adult patients with septic shock admitted to a general intensive care unit were included. Transthoracic echocardiography was performed on the first day, and repeated during and after ICU stay. Laboratory and clinical data and data on outcome were collected daily from admission and up to 7 days, shorter in cases of death or ICU discharge. The correlation of GLPS to left ventricular systolic and diastolic function parameters, cardiac biomarkers and clinical data were compared using Spearman's correlation test and linear regression analysis, and the ability of GLPS to predict outcome was evaluated using a logistic regression model. RESULTS: On the day of admission, there was a strong correlation and co-linearity of GLPS to left ventricular ejection fraction (LVEF), mitral annular motion velocity (é) and to amino-terminal pro-brain natriuretic peptide (NT-proBNP) (Spearman's ρ -0.70, -0.53 and 0.54, and R(2) 0.49, 0.20 and 0.24, respectively). In LVEF and NT-proBNP there was a significant improvement during the study period (analysis of variance (ANOVA) with repeated measures, p = 0.05 and p < 0.001, respectively), but not in GLPS, which remained unchanged over time (p = 0.10). GLPS did not correlate to the improvement in clinical characteristics over time, did not differ significantly between survivors and non-survivors (-17.4 (-20.5-(-13.7)) vs. -14.7 (-19.0 - (-10.6)), p = 0.11), and could not predict mortality. CONCLUSIONS: GLPS is frequently reduced in septic shock patients, alone or in combination with reduced LVEF and/or é. It correlates with LVEF, é and NT-proBNP, and remains affected over time. GLPS may provide further understanding on the character of myocardial dysfunction in septic shock.

Variability in echocardiographic measurements of left ventricular function in septic shock patients.

BACKGROUND: Echocardiography is increasingly used for haemodynamic evaluation and titration of therapy in intensive care, warranting reliable and reproducible measurements. The aim of this study was to evaluate the observer dependence of echocardiographic findings of left ventricular (LV) diastolic and systolic dysfunction in patients with septic shock. METHODS: Echocardiograms performed in 47 adult patients admitted with septic shock to a general intensive care unit (ICU) were independently evaluated by one cardiologist and one intensivist for the following signs: decreased diastolic tissue velocity of the base of the LV septum (é), increased early mitral inflow (E) to é ratio (E/é), decreased LV ejection fraction (EF) and decreased LV global longitudinal peak strain (GLPS). Diastolic dysfunction was defined as é <8.0 cm/s and/or E/é ≥15 and systolic dysfunction as EF <50% and/or GLPS > -15%. Ten randomly selected examinations were re-analysed two months later. Pearson's r was used to test the correlation and Bland-Altman plots to assess the agreement between observers. Kappa statistics were used to test the consistency between readers and intraclass correlation coefficients (ICC) for inter- and intraobserver variability. RESULTS: In 44 patients (94%), image quality was sufficient for echocardiographic measurements. The agreement between observers was moderate (k = 0.60 for é, k = 0.50 for E/é and k = 0.60 for EF) to good (k = 0.71 for GLPS). Pearson's r was 0.76 for é, 0.85 for E/é, 0.78 for EF and 0.84 for GLPS (p < 0.001 for all four). The ICC between observers for é was very good (0.85; 95% confidence interval (CI) 0.73-0.92), good for E/é (0.70; 95% CI 0.45 - 0.84), very good for EF (0.87; 95% CI 0.77 - 0.93), excellent for GLPS (0.91; 95% CI 0.74 - 0.95), and very good for all measures repeated by one of the observers. On Bland-Altman analysis, the mean differences and 95% limits of agreement for é, E/é, EF and GLPS were -0.01 (0.04 - 0.07), 2.0 (-14.2 - 18.1), 0.86 (-16 - 14.3) and 0.04 (-5.04 - 5.12), respectively. CONCLUSIONS: Moderate observer-related differences in assessing LV dysfunction were seen. GLPS is the least user dependent and most reproducible echocardiographic measurement of LV function in septic shock.

Amino-terminal pro-brain natriuretic peptide as a predictor of outcome in patients admitted to intensive care. A prospective observational study.

CONTEXT: Amino-terminal pro-brain-type natriuretic peptide is known to predict outcome in patients with heart failure, but its role in an intensive care setting is not yet fully established. OBJECTIVE: To assess the incidence of elevated amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) on admission to intensive care and its relation to death in the ICU and within 30 days. DESIGN: Prospective, observational cohort study. SETTING: A mixed non-cardiothoracic tertiary ICU in Sweden. PATIENTS AND MAIN OUTCOME MEASURES: NT-pro-BNP was collected from 481 consecutive patients on admission to intensive care, in addition to data on patient characteristics and outcome. A receiver-operating characteristic curve was used to identify a discriminatory level of significance, a stepwise logistic regression analysis to correct for other clinical factors and a Kaplan-Meier analysis to assess survival. The correlation between Simplified Acute Physiology Score (SAPS) 3, Sequential Organ Failure Assessment score (SOFA) and NT-pro-BNP was analysed using Spearman's correlation test. Quartiles of NT-pro-BNP elevation were compared for baseline data and outcome using a logistic regression model. RESULTS: An NT-pro-BNP more than 1380 ng -l on admission was an independent predictor of death in the ICU and within 30 days [odds ratio (OR) 2.6; 95% confidence interval (CI), 1.5 to 4.4] and was present in 44% of patients. Thirty-three percent of patients with NT-pro-BNP more than 1380 ng -1, and 14.6% of patients below that threshold died within 30 days (log rank P=0.005). NT-pro-BNP correlated moderately with SAPS 3 and with SOFA on admission (Spearman's ρ 0.5552 and 0.5129, respectively). In quartiles of NT-pro-BNP elevation on admission, severity of illness and mortality increased significantly (30-day mortality 36.1%; OR 3.9; 95% CI, 2.0 to 7.3 in the quartile with the highest values, vs. 12.8% in the lowest quartile). CONCLUSION: We conclude that NT-pro-BNP is commonly elevated on admission to intensive care, that it increases with severity of illness and that it is an independent predictor of mortality.