Hearts of stone: Rapidly progressive left ventricular myocardial calcifications in severe sepsis: Case series.

Rapidly progressive left ventricular myocardial calcification (RPLVMC) is a rare phenomenon of severe sepsis which is associated with long-term complications like irreversible cardiomyopathy and arrhythmias. To date, only 19 cases have been reported in literature. We present a case series of two patients with RPLVMC which manifested within a period of days in the setting of severe sepsis. Unique to previous case reports, the patients in the current case series had no pre-existing systemic risk factors such as end-stage kidney disease or endocrinological dysfunction. This case series aims to increase awareness of RPLVMC in severe sepsis, improve its opportunistic detection on routine medical imaging (namely chest x-ray and computed tomography), and spur future research to develop potential prevention strategies.

Echocardiography Does not Reduce Mortality in Sepsis: A Re-Evaluation Using the Medical Information Mart for Intensive Care IV Dataset.

OBJECTIVES: Echocardiography is commonly used for hemodynamic assessment in sepsis, but data regarding its association with outcome are conflicting. The aim of this study was to evaluate the association between echocardiography and outcomes in patients with septic shock using the Medical Information Mart for Intensive Care IV database. DESIGN: Retrospective cohort study comparing patients who did or did not undergo transthoracic echocardiography within the first 5 days of admission for the primary outcome of 28-day mortality. SETTING: Admissions to the Beth Israel Deaconess Medical Center intensive care from 2008 to 2019. PATIENTS: Adults 16 years old or older with septic shock requiring vasopressor support within 48 hours of admission. Readmissions and patients admitted to the coronary care unit or cardiovascular intensive care were excluded, as well as patients with ST-elevation myocardial infarction or cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Echocardiography was performed in 1,515 (27%) of 5,697 eligible admissions. The primary outcome was analyzed using a marginal structural model and rolling entry matching to adjust for baseline and time-varying confounders. Patients who underwent echocardiography showed no significant difference in 28-day mortality (adjusted hazard ratio 1.09; 95% CI, 0.95-1.25; p = 0.24). This was consistent across multiple sensitivity analyses. Secondary outcomes were changes in management instituted within 4 hours of imaging. Treatment changes occurred in 493 patients (33%) compared with 431 matched controls (29%), with the most common intervention being the administration of a fluid bolus. CONCLUSIONS: Echocardiography in sepsis was not associated with a reduction in 28-day mortality based on observational data. These findings do not negate the utility of echo in cases of diagnostic uncertainty or inadequate response to initial treatment.

Mortality in patients with septic cardiomyopathy identified by longitudinal strain by speckle tracking echocardiography: An updated systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Septic cardiomyopathy is associated with poor outcomes but its definition remains unclear. In a previous meta-analysis, left ventricular (LV) longitudinal strain (LS) showed significant prognostic value in septic patients, but findings were not robust due to a limited number of studies, differences in effect size and no adjustment for confounders. METHODS: We conducted an updated systematic review (PubMed and Scopus up to 14.02.2023) and meta-analysis to investigate the association between LS and survival in septic patients. We included studies reporting global (from three apical views) or regional LS (one or two apical windows). A secondary analysis evaluated the association between LV ejection fraction (EF) and survival using data from the selected studies. RESULTS: We included fourteen studies (1678 patients, survival 69.6%) and demonstrated an association between better performance (more negative LS) and survival with a mean difference (MD) of -1.45%[-2.10, -0.80] (p < 0.0001;I2 = 42%). No subgroup differences were found stratifying studies according to number of views used to calculate LS (p = 0.31;I2 = 16%), severity of sepsis (p = 0.42;I2 = 0%), and sepsis criteria (p = 0.59;I2 = 0%). Trial sequential analysis and sensitivity analyses confirmed the primary findings. Grade of evidence was low. In the included studies, thirteen reported LVEF and we found an association between higher LVEF and survival (MD = 2.44% [0.44,4.45]; p = 0.02;I2 = 42%). CONCLUSIONS: We confirmed that more negative LS values are associated with higher survival in septic patients. The clinical relevance of this difference and whether the use of LS may improve understanding of septic cardiomyopathy and prognostication deserve further investigation. The association found between LVEF and survival is of unlikely clinical meaning. REGISTRATION: PROSPERO number CRD42023432354.

[Research progress of critical care ultrasound in volume management of sepsis].

Critical care ultrasound has many operational advantages such as visualization, reproducibility, noninvasiveness, and real-time dynamic monitoring, and is now widely used in the treatment process of various clinical diseases. Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. On the basis of active anti-infection, early administration of fluid resuscitation to maintain organ tissue perfusion and individualized adjustment of volume management is the core of improving patient prognosis and reducing mortality. Currently, there are many shortcomings in the commonly used clinical physical examination and static parameters to assess volume status. Critical care ultrasound has many advantages in volume management of sepsis due to its diversified advantages, which promoted the development of critical care medicine. This article presents a review of critical care ultrasound in volume management in sepsis, aiming to highlight the value and limitations of the application of critical care ultrasound in volume management in sepsis.

Abdominal perfusion in canine patients with pyometra and sepsis evaluated by Doppler and contrast-enhanced ultrasound.

BACKGROUND: Sepsis is a condition characterized by organic dysfunction, leading to hemodynamic instability and high morbidity and mortality rates in humans and animals. Early identification of perfusion changes and appropriate management of sepsis are crucial for improving patient prognosis. Currently, the Systemic Inflammatory Response Syndrome (SIRS) and Sequential Organ Failure Assessment (SOFA) scores are widely studied for sepsis identification and evaluation of organ dysfunction. However, these scores do not assess gastrointestinal involvement, which is common in this condition. Contrast-enhanced ultrasound (CEUS) and Doppler have been considered promising diagnostic techniques for detecting changes in vascularization and microcirculation in a non-invasive and safe manner, particularly in the gastrointestinal system. This study aimed to evaluate duodenal perfusion using CEUS, as well as abdominal aortic and cranial mesenteric artery blood flow using Doppler ultrasound, and systolic arterial pressure (SAP) in 17 bitches with pyometra and in 10 healthy animals. RESULTS: The variables were compared between the pyometra and control groups, as well between patients with and without sepsis determined by the SOFA or SIRS scores. Pyometra was found to cause a reduction in abdominal aortic blood flow volume, aortic peak systolic velocity, and resistivity index as evaluated by Doppler ultrasound. Patients with sepsis according to the SOFA criteria only presented lower SAP. In contrast, sepsis animals identified by the SIRS score exhibited lower SAP, aortic peak systolic velocity, aortic blood flow volume, and aortic resistivity index and additionally, higher peak intensity of contrast in the duodenal wall. CONCLUSIONS: Pyometra causes a reduction in abdominal aortic blood flow, which is more pronounced in animals with sepsis identified by the SIRS criteria. These animals also exhibited a decrease in systolic blood pressure and an increase in duodenal perfusion, as evident by CEUS. However, these changes were not observed in patients with sepsis identified by the SOFA criteria. The alterations in intestinal perfusion observed in animals with sepsis indicate the presence of inflammation or dysfunction. In this regard, CEUS proves to be a valuable technique for detecting subtle changes in tissue hemodynamics that may not be apparent in conventional exams.

Assessment of systemic circulation using ultrasound Doppler in late onset neonatal sepsis and its clinical correlation: an observational study.

OBJECTIVES: To measure the Doppler velocimetry parameters in the anterior cerebral artery (ACA), superior mesenteric artery (SMA), and main renal artery (RA) in neonates with late-onset sepsis and correlate it with associated clinical morbidities. METHODOLOGY: Prospective observational study carried out at a tertiary-level neonatal intensive care unit in India in 2022, enrolling 20 neonates with late-onset neonatal sepsis (LONS). Baseline characteristics and sepsis parameters obtained. Serial ultrasound performed on days 1, 3, and 7 from the day of clinical sepsis in the ACA, SMA, and RA and velocimetry measurements obtained. The findings were compared with 20 gestational age (GA) matched neonates in the control arm. RESULTS: The mean GA of neonates with LONS was 31.03 ± 2.79 weeks and their mean birthweight was 1474 ± 509.99 g. The peak systolic velocity, resistive and pulsatility indices were significantly higher in ACA, SMA, and RA and the end-diastolic velocity was significantly lower in ACA and RA (P < 0.05) in LONS. The incidences of intraventricular hemorrhage (IVH), necrotising enterocolitis (NEC), and acute kidney injury (AKI) in neonates with LONS were 45%, 50%, and 10% respectively. A subgroup analysis of the Doppler velocimetry parameters in the neonates with LONS and for neonates with and without clinical outcomes did not suggest a significant difference. CONCLUSION: LONS is associated with alterations in cerebral, splanchnic, and renal perfusion seen as abnormal blood flow velocimetry and vascular resistance which may predispose to IVH, NEC, and AKI.

Prognostic value of Doppler waveform analysis of common femoral vein in septic patients: a prospective cohort study.

OBJECTIVES: To assess whether there is an association between abnormal common femoral vein (CFV) Doppler waveform and intensive care unit (ICU) mortality in patients with sepsis. METHODS: Patients admitted to the ICU with sepsis were included. Pulsed-wave Doppler was performed by examining the CFV in the short axis without angle correction and in the long axis with angle correction. An abnormal CFV Doppler waveform was determined by a retrograde velocity peak (RVP) > 10 cm/s in the long axis or RVP > 50% of the antegrade velocity peak in the short axis. TAPSE < 17 mm was defined as right ventricular (RV) dysfunction. The primary outcome was ICU mortality. RESULTS: One hundred and ten patients were included. There was no association between abnormal CFV Doppler waveforms in the long (p = 0.709) and short axes (p = 0.171) and ICU mortality. TAPSE measurements were performed in 16 patients. RV dysfunction was identified in 8 (50.0%) patients. There was no association between the diagnosis of RV dysfunction based on TAPSE measurement and the identification of abnormal CFV Doppler waveforms in the long axis (p = 1.000) and in the short axis (p = 1.000). CONCLUSION: Abnormal CFV Doppler waveforms were not associated with ICU mortality in patients with sepsis. Furthermore, in the exploratory analysis, these alterations were not useful in identifying RV dysfunction in these patients.

Quantitative evaluation of myocardial layer-specific strain using two-dimensional speckle tracking echocardiography in septic patients.

BACKGROUND: Although global longitudinal strain (GLS) is proven to be reduced and associated with adverse outcomes in septic patients, it has not been elucidated whether or not layer-specific strains are reduced. We aimed to explore the layer-specific strains of left ventricular (LV) for assessing myocardial dysfunction in septic patients. METHODS: A prospective observational study of patients with sepsis was conducted in a tertiary hospital in China. Routine two-dimensional speckle tracking echocardiography was performed within 24 h of enrollment. Demographic data, laboratory values, and clinical outcomes were collected. RESULTS: We recruited 79 septic patients finally. The mean age of septic patients was 59.4 years old and 45 (57.0%) were male. The median Acute Physiology Age and Chronic Health Evaluation (APACHE II) score, and mean sequential organ failure assessment (SOFA) score of all patients were 19.0 and 7.7, respectively. According to the left ventricular ejection fraction (LVEF) value of 50%, the patients were categorized into two groups: SICM (sepsis-induced cardiomyopathy, LVEF < 50%, n = 22) and non-SICM group ( LVEF ≥ 50%, n = 57). The median LVEF of SICM and non-SICM patients were 41.9% and 58.7%, and SICM patients had less negative layer-specific strain and global strain than that of non-SICM patients. The echocardiographic comparison of non-SICM and healthy controls was conducted to explore the myocardial injuries of non-SICM patients and the non-SICM had worse LS-epi than that of controls (-18.5% vs. -21.4%, p = 0.024). CONCLUSION: There were 72.2% (57) septic patients presented with non-SICM (LVEF ≥ 50%), and the strain value of epicardium of them was less negative than healthy controls.

Association between intrarenal venous flow from Doppler ultrasonography and acute kidney injury in patients with sepsis in critical care: a prospective, exploratory observational study.

BACKGROUND: Intrarenal venous flow (IRVF) patterns assessed using Doppler renal ultrasonography are real-time bedside visualizations of renal vein hemodynamics. Although this technique has the potential to detect renal congestion during sepsis resuscitation, there have been few studies on this method. We aimed to examine the relationship between IRVF patterns, clinical parameters, and outcomes in critically ill adult patients with sepsis. We hypothesized that discontinuous IRVF was associated with elevated central venous pressure (CVP) and subsequent acute kidney injury (AKI) or death. METHODS: We conducted a prospective observational study in two tertiary-care hospitals, enrolling adult patients with sepsis who stayed in the intensive care unit for at least 24 h, had central venous catheters placed, and received invasive mechanical ventilation. Renal ultrasonography was performed at a single time point at the bedside after sepsis resuscitation, and IRVF patterns (discontinuous vs. continuous) were confirmed by a blinded assessor. The primary outcome was CVP obtained at the time of renal ultrasonography. We also repeatedly assessed a composite of Kidney Disease Improving Global Outcomes of Stage 3 AKI or death over the course of a week as a secondary outcome. The association of IRVF patterns with CVP was examined using Student's t-test (primary analysis) and that with composite outcomes was assessed using a generalized estimating equation analysis, to account for intra-individual correlations. A sample size of 32 was set in order to detect a 5-mmHg difference in CVP between IRVF patterns. RESULTS: Of the 38 patients who met the eligibility criteria, 22 (57.9%) showed discontinuous IRVF patterns that suggested blunted renal venous flow. IRVF patterns were not associated with CVP (discontinuous flow group: mean 9.24 cm H2O [standard deviation: 3.19], continuous flow group: 10.65 cm H2O [standard deviation: 2.53], p = 0.154). By contrast, the composite outcome incidence was significantly higher in the discontinuous IRVF pattern group (odds ratio: 9.67; 95% confidence interval: 2.13-44.03, p = 0.003). CONCLUSIONS: IRVF patterns were not associated with CVP but were associated with subsequent AKI in critically ill adult patients with sepsis. IRVF may be useful for capturing renal congestion at the bedside that is related to clinical patient outcomes.

Interdisciplinary perspectives on computed tomography in sepsis: survey among medical doctors at a large university medical center.

OBJECTIVES: This study aims to describe physicians' perspectives on the use of computed tomography (CT) in patients with sepsis. METHODS: In January 2022, physicians of a large European university medical center were surveyed using a web-based questionnaire asking about their views on the role of CT in sepsis. A total of 371 questionnaires met the inclusion criteria and were analyzed using work experience, workplace, and medical specialty of physicians as variables. Chi-square tests were performed. RESULTS: Physicians considered the ability to detect an unknown focus as the greatest benefit of CT scans in sepsis (70.9%, n = 263/371). Two clinical criteria - "signs of decreased vigilance" (89.2%, n = 331/371) and "increased catecholamine demand" (84.7%, n = 314/371) - were considered highly relevant for a CT request. Elevated procalcitonin (82.7%, n = 307/371) and lactate levels (83.6%, n = 310/371) were consistently found to be critical laboratory values to request a CT. As long as there is evidence of infection in one organ region, most physicians (42.6%, n = 158/371) would order a CT scan based on clinical assessment. Combined examination of the chest, abdomen, and pelvis was favored (34.8%, n = 129/371) in cases without clinical clues of an infection source. A time window of ≥ 1-6 h was preferred for both CT examinations (53.9%, n = 200/371) and CT-guided interventions (59.3%, n = 220/371) in patients with sepsis. CONCLUSION: Despite much consensus, there are significant differences in attitudes towards the use of CT in septic patients among physicians from different workplaces and medical specialties. Knowledge of these perspectives may improve patient management and interprofessional communication. KEY POINTS: Despite interdisciplinary consensus on the use of CT in sepsis, statistically significant differences in the responses are apparent among physicians from different workplaces and medical specialties. The detection of a previously unknown source of infection and the ability to plan interventions and/or surgery based on CT findings are considered key advantages of CT in septic patients. Timing of CT reflects the requirements of specific disciplines.

The clinical application of ultrasound for acute kidney injury during sepsis-from macroscopic to microscopic renal perfusion perspectives.

OBJECTIVE: The aim was to quantify macroscopic renal blood flow and renal cortical microcirculation in patients with septic acute kidney injury (AKI) using ultrasound and contrast-enhanced ultrasound. METHODS: In this case-control study, patients in the intensive care unit diagnosed with septic AKI were divided into stages 1-3 based on the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) AKI diagnostic criteria. The patients were categorized into mild (stage 1) and severe (stages 2 and 3) groups, while septic patients without AKI served as the control group. Ultrasound parameters such as macrovascular renal blood flow and time-averaged velocity, as well as cardiac function parameters such as cardiac output and cardiac index, were measured. The time-intensity curve in the microcirculation was analyzed through contrast-enhanced ultrasound imaging software to calculate imaging parameters such as peak time, rise time, fall half-time and mean transit time of the interlobar arteries in the renal cortex. RESULTS: In terms of macrocirculation, renal blood flow and time-averaged velocity decreased gradually with the progression of septic acute renal injury (p = 0.004, p < 0.001). There was no difference in cardiac output and cardiac index values among the three groups (p = 0.17 and p = 0.12). In terms of microcirculation, ultrasonic Doppler parameters of the renal cortical interlobular artery, such as peak intensity, risk index and ratio of peak systolic velocity to end-diastolic velocity, gradually increased (all p values <0.05). The temporal contrast-enhanced ultrasound parameters-time to peak, rise time, fall half-time and mean transit time-were prolonged in AKI groups when compared with the control group (p < 0.001, p = 0.003, p = 0.004 and p = 0.009, respectively). CONCLUSION: In patients with septic AKI, the renal blood flow and time average velocity of macrocirculation in the kidneys are reduced, while the time parameters of microcirculation such as time to peak, rise time, fall half-time and mean transit time are prolonged, especially in patients with severe AKI. These changes are not related to changes in cardiac output or cardiac index.

Prognostic Value of Vertebral Bone Density in the CT Scans of Sepsis Patients Admitted to the Intensive Care Unit.

AIM: To evaluate the prognostic value of vertebral bone mineral density (BMD) and its relationship with mortality using the computed tomography (CT) scans of sepsis patients admitted to the intensive care unit. METHODS: In this retrospective study, patients diagnosed with sepsis at the intensive care unit between January and December 2022 were evaluated. Bone density was manually measured from the vertebral body using axial CT images. The relationship of clinical variables and patient outcomes with vertebral BMD, mortality, and mechanical ventilation was investigated. A lower BMD (osteoporosis) was defined as ≤100 HU. RESULTS: The study included 213 patients (95 females, 44.6%). The mean age of all patients was 60.1±18.7 years. At least one comorbidity was present in 64.7% (n=138) of the patients, and the most common comorbidity was hypertension (n=73, 34.2%). The mortality rate was 21.1% (n=45), and the mechanical ventilation rate was 17.4% (n=37), both being statistically significantly higher among the patients with a lower BMD (36.4 vs. 12.9%; p<0.001 and 29.7 vs. 10.8%; p=0.001, respectively). The rate of a lower BMD was significantly higher in the mortality group (59.5 vs. 29.5%; p=0.001). In the regression analysis, a lower BMD [odds ratio (OR), 2.785; 95% confidence interval (CI): 1.231-6.346, p=0.014] was a significant independent predictor of mortality. Interobserver agreement for BMD measurement was excellent, with an intraclass correlation coefficient of 0.919 (95% CI: 0.904-0.951). CONCLUSION: Vertebral BMD is a strong independent predictor of mortality and can be easily and reproducible evaluated on the thoracoabdominal CT images of patients admitted to the intensive care unit with a diagnosis of sepsis.

Point-of-Care Ultrasound: A Multimodal Tool for the Management of Sepsis in the Emergency Department.

Sepsis and septic shock are life-threatening emergencies associated with increased morbidity and mortality. Hence, early diagnosis and management of both conditions is of paramount importance. Point-of-care ultrasound (POCUS) is a cost-effective and safe imaging modality performed at the bedside, which has rapidly emerged as an excellent multimodal tool and has been gradually incorporated as an adjunct to physical examination in order to facilitate evaluation, diagnosis and management. In sepsis, POCUS can assist in the evaluation of undifferentiated sepsis, while, in cases of shock, it can contribute to the differential diagnosis of other types of shock, thus facilitating the decision-making process. Other potential benefits of POCUS include prompt identification and control of the source of infection, as well as close haemodynamic and treatment monitoring. The aim of this review is to determine and highlight the role of POCUS in the evaluation, diagnosis, treatment and monitoring of the septic patient. Future research should focus on developing and implementing a well-defined algorithmic approach for the POCUS-guided management of sepsis in the emergency department setting given its unequivocal utility as a multimodal tool for the overall evaluation and management of the septic patient.

Perfusion and T2 Relaxation Time as Predictors of Severity and Outcome in Sepsis-Associated Acute Kidney Injury: A Preclinical MRI Study.

BACKGROUND: Preventing sepsis-associated acute kidney injury (S-AKI) can be challenging because it develops rapidly and is often asymptomatic. Probability assessment of disease progression for therapeutic follow-up and outcome are important to intervene and prevent further damage. PURPOSE: To establish a noninvasive multiparametric MRI (mpMRI) tool, including T1 , T2 , and perfusion mapping, for probability assessment of the outcome of S-AKI. STUDY TYPE: Preclinical randomized prospective study. ANIMAL MODEL: One hundred and forty adult female SD rats (65 control and 75 sepsis). FIELD STRENGTH/SEQUENCE: 9.4T; T1 and perfusion map (FAIR-EPI) and T2 map (multiecho RARE). ASSESSMENT: Experiment 1: To identify renal injury in relation to sepsis severity, serum creatinine levels were determined (31 control and 35 sepsis). Experiment 2: Animals underwent mpMRI (T1 , T2 , perfusion) 18 hours postsepsis. A subgroup of animals was immediately sacrificed for histology examination (nine control and seven sepsis). Result of mpMRI in follow-up subgroup (25 control and 33 sepsis) was used to predict survival outcomes at 96 hours. STATISTICAL TESTS: Mann-Whitney U test, Spearman/Pearson correlation (r), P < 0.05 was considered statistically significant. RESULTS: Severely ill septic animals exhibited significantly increased serum creatinine levels compared to controls (70 ± 30 vs. 34 ± 9 µmol/L, P < 0.0001). Cortical perfusion (480 ± 80 vs. 330 ± 140 mL/100 g tissue/min, P < 0.005), and cortical and medullary T2 relaxation time constants were significantly reduced compared to controls (41 ± 4 vs. 37 ± 5 msec in cortex, P < 0.05, 52 ± 7 vs. 45 ± 6 msec in medulla, P < 0.05). The combination of cortical T2 relaxation time constants and perfusion results at 18 hours could predict survival outcomes at 96 hours with high sensitivity (80%) and specificity (73%) (area under curve of ROC = 0.8, Jmax = 0.52). DATA CONCLUSION: This preclinical study suggests combined T2 relaxation time and perfusion mapping as first line diagnostic tool for treatment planning. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Texture Feature-Based Machine Learning Classification on MRI Image for Sepsis-Associated Encephalopathy Detection: A Pilot Study.

Objective: The objective of this study was to assess the performance of combining MRI-based texture analysis with machine learning for differentiating sepsis-associated encephalopathy (SAE) from sepsis alone. Method: Sixty-six MRI-T1WI images of an SAE patient and 125 images of patients with sepsis alone were collected. Frontal lobe, brain stem, hippocampus, and amygdala were selected as regions of interest (ROIs). 279 texture features of each ROI were obtained using MaZda software. After the dimension reduction, 30 highly discriminative features of each ROI were adopted to differentiate SAE from sepsis alone using the CatBoost model. Results: The classification models of frontal, brain stem, hippocampus, and amygdala were constructed. The classification accuracy was above 0.83, and the area under the curve (AUC) exceeded 0.90 in the validation set. Conclusion: The texture features differed between SAE patients and patients with sepsis alone in different anatomical locations, suggesting that MRI-based texture analysis with machine learning might be helpful in differentiating SAE from sepsis alone.