Onset Of Septic Shock Research Articles

Comparison of Modified Early Warning Score (MEWS), Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) for early prediction of septic shock in diabetic patients in Emergency Departments

IntroductionSepsis is a severe medical condition that can be life-threatening. If sepsis progresses to septic shock, the mortality rate increases to around 40%, much higher than the 10% mortality observed in sepsis. Diabetes increases infection and sepsis risk, making management complex. Various scores of screening tools, such as Modified Early Warning Score (MEWS), Simplified Acute Physiology Score (SAPS II), Sequential Organ Failure Assessment Score (SOFA), and Acute Physiology and Chronic Health Evaluation (APACHE II), are used to predict the severity or mortality rate of disease. Our study aimed to compare the effectiveness and optimal cutoff points of these scores. We focused on the early prediction of septic shock in patients with diabetes in the Emergency Department (ED).MethodsWe conducted a retrospective cohort study to collect data on patients with diabetes. We collected prediction factors and MEWS, SOFA, SAPS II and APACHE II scores to predict septic shock in these patients. We determined the optimal cutoff points for each score. Subsequently, we compared the identified scores with the gold standard for diagnosing septic shock by applying the Sepsis-3 criteria.ResultsSystolic blood pressure (SBP), peripheral oxygen saturation (SpO2), Glasgow Coma Scale (GCS), pH, and lactate concentrations were significant predictors of septic shock (p < 0.001). The SOFA score performed well in predicting septic shock in patients with diabetes. The area under the receiver operating characteristics (ROC) curve for the SOFA score was 0.866 for detection within 48 h and 0.840 for detection after 2 h of admission to the ED, with the optimal cutoff score of ≥ 6.ConclusionSBP, SpO2, GCS, pH, and lactate concentrations are crucial for the early prediction of septic shock in patients with diabetes. The SOFA score is a superior predictor for the onset of septic shock in patients with diabetes compared with MEWS, SAPS II, and APACHE II scores. Specifically, a cutoff of ≥ 6 in the SOFA score demonstrates high accuracy in predicting shock within 48 h post-ED visit and as early as 2 h after ED admission.

Relationship between thrombocytopenia and prognosis in children with septic shock: a retrospective cohort study

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 109/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 109/L had a higher 28-day mortality rate (63.6% vs. 45%, p = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04–1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95–0.99; p = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia (p value from the log-rank test, p = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.

Effects of metaraminol and norepinephrine on hemodynamics and kidney function in a miniature pig model of septic shock.

To compare the effects of metaraminol and norepinephrine on hemodynamics and kidney injury in the treatment of septic shock, and calculate the conversion dose ratio between the two vasopressors. This randomized controlled study was performed on 15 Guizhou miniature pigs. Septic shock was induced by fecal peritonitis in 10 animals, and 5 were used as a sham-operated group (shams). Fluid resuscitation and vasopressors were initiated 30 min after the onset of septic shock. The septic shock pigs were randomly assigned to receive one of the two drugs to restore and maintain mean arterial pressure (MAP) ≥ 65 mmHg for 3 h. Hemodynamics and heart rate were continuously monitored. There was no significant difference in MAP, heart rate, cardiac output (CO) and central venous pressure (CVP) between the two groups after treatment. No arrhythmias such as atrial fibrillation and ventricular fibrillation presented during continuous monitoring. After septic shock, the animals showed obvious kidney injury. In addition, compared with norepinephrine, the creatinine at 3 h was significantly lower with metaraminol. According to propensity score matching, the ratio of 6: 1 was considered appropriate for the dose equivalence calculation of metaraminol (μg·kg-1·min-1): norepinephrine (μg·kg-1·min-1). Metaraminol has a similar pressor effect to norepinephrine in septic shock; it does not increase heart rate and aggravate kidney injury after shock compared with norepinephrine. And our research may provide some laboratory evidence for the clinical usage of metaraminol.

Emerging Toxicities of Antibody-Drug Conjugates for Breast Cancer: Clinical Prioritization of Adverse Events from the FDA Adverse Event Reporting System.

Antibody-drug conjugates (ADCs) are gaining widespread use in the treatment of breast cancer, although toxicity remains an underexplored issue in the real-world clinical setting. Individual case safety reports collected in large pharmacovigilance databases can advance our knowledge on their safety profile in routine clinical practice. We prioritized adverse events (AEs) reported with ADCs approved for breast cancer using the Food andDrugAdministration Adverse Event Reporting System (FAERS). We assessed clinical priority of AEs reported in FAERS (February 2013-March 2022) for trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG) by attributing a score to each AE disproportionally reported with ADCs. Four criteria were assessed: clinical relevance, reporting rate, reported case fatality rate, and stability of disproportionality signals (consistency of the reporting odds ratio across multiple analyses using three different comparators). We retained 6589 reports (77.4% referring to T-DM1 as suspect), and 572 AEs generated a disproportionality signal in at least one analysis. The majority of these AEs (62%) were classified as moderate clinical priorities (e.g., interstitial lung disease with T-DXd, thrombocytopenia, peripheral neuropathy with T-DM1, febrile neutropenia, and large intestine perforation with SG). Three AEs emerged as high clinical priorities (6 points): septic shock and neutropenic colitis with SG (N = 8 and 13, with median onset 13 and 10 days, respectively), without co-reported immunosuppressive agents; and pulmonary embolism with T-DM1 (N = 31, median onset 109 days, 52% with reported metastasis). The heterogeneous spectrum of post-marketing toxicities for ADCs used in breast cancer, as emerging from the FAERS, is largely in line with preapproval evidence. Although causality cannot be proved, we call for increased awareness by oncologists on potential serious unexpected reactions, including early onset of septic shock and neutropenic colitis with SG, and late emergence of pulmonary embolism with T-DM1.

Focused Cardiac Ultrasound Findings of Fluid Tolerance and Fluid Resuscitation in Septic Shock.

Compliance with the fluid bonus component of the SEP-1 (severe sepsis and septic shock management) bundle remains poor due to concerns for iatrogenic harm from fluid overload. We sought to assess whether patients who received focused cardiac ultrasound (FCU) and were found to be fluid tolerant (FT) were more likely to receive the recommended 30 mL/kg fluid bolus within 3 hours of sepsis identification. Retrospective, observational cohort study. University-affiliated, tertiary-care hospital in the United States. Emergency department patients presenting with septic shock from 2018 to 2021. The primary exposure was receipt of FCU with identification of fluid tolerance 3 hours from onset of septic shock. None. Two hundred ninety-two of 1,024 patients with septic shock received FCU within 3 hours of sepsis onset. One hundred seventy-seven were determined to be FT. One hundred fifteen patients were determined to have poor fluid tolerance (pFT). FT patients were more likely to reach the recommended 30 mL/kg fluid bolus amount compared with pFT (FT 52.0% vs. pFT 31.3%, risk difference: 20.7%, [95% CI, 9.4-31.9]). Patients who did not receive FCU met the bolus requirement 34.3% of the time. FT patients received more fluid within 3 hours (FT 2,271 mL vs. pFT 1,646 mL, mean difference 625 mL [95% CI, 330-919]). Multivariable logistic regression was used to estimate the association between fluid tolerance FCU findings and compliance with 30 mL/kg bolus after adjustment for patient characteristics and markers of hemodynamic instability. FT with associated with a higher likelihood of meeting bolus requirement (odds ratio 2.17 [1.52-3.12]). Patients found to be FT by FCU were more likely to receive the recommended 30 mL/kg bolus in the SEP-1 bundle when compared with patients found with pFT or those that did not receive FCU. There was no difference between groups in 28-day mortality, vasopressor requirement, or need for mechanical ventilation.

High versus standard blood pressure target in hypertensive high-risk patients undergoing elective major abdominal surgery: a study protocol for the HISTAP randomized clinical trial

BackgroundThe intraoperative period is often characterized by hemodynamic instability, and intraoperative hypotension is a common complication. The optimal mean arterial pressure (MAP) target in hypertensive patients is still not clear. We hereby describe the protocol and detailed statistical analysis plan for the high versus standard blood pressure target in hypertensive high-risk patients undergoing elective major abdominal surgery: the HISTAP randomized clinical trial. The HISTAP trial aims at addressing whether the use of a higher intraoperative MAP target in high-risk hypertensive surgical patients scheduled for elective abdominal surgery would improve postoperative outcomes, as compared to the standard and recommended perioperative MAP, by using a composite outcome including a 30-day mortality from surgical intervention and at least one major organ dysfunction or new onset of sepsis and septic shock occurring 7 days after surgery.MethodsThe HISTAP trial is an investigator-initiated, pragmatic, parallel-grouped, randomized, stratified, analyst-blinded trial with adequate allocation sequence generation, and allocation concealment. We will allocate 636 patients to a MAP target ≥ 80 mmHg (treatment group) or to a MAP target ≥65 mmHg (control group). The primary outcome is a composite outcome including a 30-day mortality from the operation and major organ complications. Secondary outcomes are mortality at 30 days, intensive care unit (ICU) length of stay, ICU readmission, Sequential Organ Failure Assessment (SOFA) scores recorded up to postoperative day 7, overall intraoperative fluid balance, vasopressors use, and the need for reoperation. An unadjusted χ2 test will be used for the primary outcome analysis. A Cox proportional hazards model will be used to adjust the association between the primary outcome and baseline covariates.ConclusionsThe HISTAP trial results will provide important evidence to guide clinicians’ choice regarding the intraoperative MAP target in high-risk hypertensive patients scheduled for elective abdominal surgery.

Development and Validation of Deep-Learning-Based Sepsis and Septic Shock Early Prediction System (DeepSEPS) Using Real-World ICU Data.

Successful sepsis treatment depends on early diagnosis. We aimed to develop and validate a system to predict sepsis and septic shock in real time using deep learning. Clinical data were retrospectively collected from electronic medical records (EMRs). Data from 2010 to 2019 were used as development data, and data from 2020 to 2021 were used as validation data. The collected EMRs consisted of eight vital signs, 13 laboratory data points, and three demographic information items. We validated the deep-learning-based sepsis and septic shock early prediction system (DeepSEPS) using the validation datasets and compared our system with other traditional early warning scoring systems, such as the national early warning score, sequential organ failure assessment (SOFA), and quick sequential organ failure assessment. DeepSEPS achieved even higher area under receiver operating characteristic curve (AUROC) values (0.7888 and 0.8494 for sepsis and septic shock, respectively) than SOFA. The prediction performance of traditional scoring systems was enhanced because the early prediction time point was close to the onset time of sepsis; however, the DeepSEPS scoring system consistently outperformed all conventional scoring systems at all time points. Furthermore, at the time of onset of sepsis and septic shock, DeepSEPS showed the highest AUROC (0.9346). The sepsis and septic shock early warning system developed in this study exhibited a performance that is worth considering when predicting sepsis and septic shock compared to other traditional early warning scoring systems. DeepSEPS showed better performance than existing sepsis prediction programs. This novel real-time system that simultaneously predicts sepsis and septic shock requires further validation.

INITIATION TIMING OF VASOPRESSOR IN PATIENTS WITH SEPTIC SHOCK: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and meta-analysis to explore its initiation timing for septic shock patients. Methods: PubMed, Cochrane Library, Embase, and Web of Sciences were searched from inception to July 12, 2023, for relevant studies. Primary outcome was short-term mortality. Meta-analysis was performed using Stata 15.0. Results: Twenty-three studies were assessed, including 2 randomized controlled trials and 21 cohort studies. The early group resulted in lower short-term mortality than the late group (OR [95% CI] = 0.775 [0.673 to 0.893], P = 0.000, I2 = 67.8%). The significance existed in the norepinephrine and vasopressin in subgroup analysis. No significant difference was considered in the association between each hour's vasopressor delay and mortality (OR [95% CI] = 1.02 [0.99 to 1.051], P = 0.195, I2 = 57.5%). The early group had an earlier achievement of target MAP ( P < 0.001), shorter vasopressor use duration ( P < 0.001), lower serum lactate level at 24 h ( P = 0.003), lower incidence of kidney injury ( P = 0.001), renal replacement therapy use ( P = 0.022), and longer ventilation-free days to 28 days ( P < 0.001). Conclusions: Early initiation of vasopressor (1-6 h within septic shock onset) would be more beneficial to septic shock patients. The conclusion needs to be further validated by more well-designed randomized controlled trials.

The effect of fluid therapy during the first 12 hours after septic shock onset in pediatric patients

The effect of fluid therapy during the first 12 hours after septic shock onset in pediatric patients

Effect of early vasopressin combined with norepinephrine on short-term mortality in septic shock: A retrospective study based on the MIMIC-IV database

BackgroundSeptic shock is a leading cause of death in intensive care units (ICUs), with short-term mortality rates of 35–40%. Vasopressin (AVP) is a second-line vasoactive agent for septic shock, and recent studies suggest that early AVP use can be beneficial. However, differences between early initiation of AVP combined with norepinephrine (NE) and nonearly AVP with NE are unclear. A retrospective cohort research was designed to explore the effects of early AVP initiation versus nonearly AVP initiation. MethodsThis retrospective single-center cohort study included adult patients with septic shock from the MIMIC (Medical Information Mart for Intensive Care)-IV database. According to whether AVP was used early in the ICU (intensive care unit), patients were assigned to the early- (within 6 h of septic shock onset) and non-early-AVP (at least 6 h after septic shock onset) groups. The primary outcome was 28-day mortality. The secondary outcomes were ICU and hospital mortality, the numbers of vasopressor-free and ventilation-free days at 28 days, ICU length of stay (LOS), hospital LOS, sequential organ failure assessment (SOFA) score on days 2 and 3, and renal replacement therapy (RRT) use on days 2 and 3. Univariate and multivariate cox proportional-hazards regression, propensity-score matching were used to analyze the differences between the groups. ResultsThe study included 531 patients with septic shock: 331 (62.5%) in the early-AVP group and 200 (37.5%) in the non-early-AVP group. For 1:1 matching, 158 patients in the early-AVP group were matched with the same number of patients with nonearly AVP. Regarding the primary outcome, there was no significant difference between the early- and non-early-AVP groups in 28-day mortality (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.68–1.24). For the secondary outcomes, there were no differences between the early- and non-early-AVP groups in ICU mortality (HR = 0.95, 95% CI = 0.67–1.35), hospital mortality (HR = 0.95, 95% CI = 0.69–1.31), the numbers of vasopressor-free and ventilation-free days at 28 days, ICU LOS, hospital LOS, SOFA score on days 2 and 3, and RRT use on days 2 and 3. ConclusionsThere was no difference in short-term mortality between early AVP combined with NE and nonearly AVP with NE in septic shock.

Diagnosis and treatment of pediatric septic shock in pediatric intensive care units from hospitals of different levels

Objective: To investigate the differences in clinical characteristics, diagnosis, and treatment of pediatric septic shock in pediatric intensive care unit (PICU) among hospitals of different levels. Methods: This retrospective study enrolled 368 children with septic shock treated in the PICU of Beijing Children's Hospital, Henan Children's Hospital, and Baoding Children's Hospital from January 2018 to December 2021. Their clinical data were collected, including the general information, location of onset (community or hospital-acquired), severity, pathogen positivity, consistence of guideline (the rate of standard attainment at 6 h after resuscitation and the rate of anti-infective drug administration within 1 h after diagnosis), treatment, and in-hospital mortality. The 3 hospitals were national, provincial, and municipal, respectively. Furthermore, the patients were divided into the tumor group and the non-tumor group, and into the in-hospital referral group and the outpatient or emergency admission group. Chi-square test and Mann-Whitney U test were used to analyze the data. Results: The 368 patients aged 32 (11, 98) months, of whom 223 were males and 145 females. There were 215, 107, and 46 patients with septic shock, with males of 141, 51, and 31 cases, from the national, provincial, and municipal hospitals, respectively. The difference in pediatric risk of mortality Ⅲ (PRISM Ⅲ) scores among the national,provincial and municipal group was statistically significant (26(19, 32) vs.19(12, 26) vs. 12(6, 19), Z=60.25,P<0.001). The difference in community acquired septic shock among the national,provincial and municipal group was statistically significant (31.6%(68/215) vs. 84.1%(90/107) vs. 91.3%(42/46), χ2=108.26,P<0.001). There were no significant differences in compliance with guidelines among the 3 groups (P>0.05). The main bacteria detected in the national group were Klebsiella pneumoniae (15.4% (12/78)) and Staphylococcus aureus (15.4% (12/78)); in the provincial group were Staphylococcus aureus (19.0% (12/63)) and Pseudomonas aeruginosa (12.7% (8/63)), and in the municipal group were Streptococcus pneumoniae (40.0% (10/25)) and Enteric bacilli (16.0% (4/25)). The difference in the proportion of virus and the proportion of 3 or more initial antimicrobials used among the national,provincial and municipal group was statistically significant (27.7% (43/155) vs. 14.9% (13/87) vs. 9.1% (3/33), 22.8%(49/215) vs. 11.2%(12/107) vs. 6.5%(3/46), χ2=8.82, 10.99, both P<0.05). There was no difference in the in-hospital mortality among the 3 groups (P>0.05). Regarding the subgroups of tumor and non-tumor, the national group had higher PRISM Ⅲ (31(24, 38) vs. 22 (21, 28) vs.16 (9, 22), 24 (18, 30) vs. 17(8, 24) vs. 10 (5, 16), Z=30.34, 10.45, both P<0.001), and it was the same for the subgroups of in-hospital referral and out-patient or emergency admission (29 (21, 39) vs. 23 (17, 30) vs. 15 (10, 29), 23 (17, 29) vs. 18 (10, 24) vs. 11 (5, 16), Z=20.33, 14.25, both P<0.001) as compared to the provincial and municipal group. There was no significant difference in the in-hospital mortality among the 2 pairs of subgroups (all P>0.05). Conclusion: There are differences in the severity, location of onset, pathogen composition, and initial antibiotics of pediatric septic shock in children's hospitals of different levels, but no differences in compliance with guidelines and in-hospital survival rate.

Understanding the Role of Ureteral Access Sheath in Preventing Post-Operative Infectious Complications in Stone Patients Treated with Ureteroscopy and Ho:YAG Laser Lithotripsy: Results from a Tertiary Care Referral Center.

The use of ureteral access sheaths (UAS) limits the irrigation-induced increase in intrarenal pressure during ureteroscopy (URS). We investigated the relationship between UAS and rates of postoperative infectious complications in stone patients treated with URS. Data from 369 stone patients treated with URS from September 2016 to December 2021 at a single institution were analyzed. UAS (10/12 Fr) placement was attempted in case of intrarenal surgery. The chi-square test was used to assess the relationship between the use of UAS and fever, sepsis, and septic shock. Univariable and multivariable logistic regression analyses tested the association of patients' characteristics and operative data and the rate of postoperative infectious complications. Full data collection of 451 URS procedures was available. Overall, UAS was used in 220 (48.8%) procedures. As for postoperative infectious sequalae, we recorded fever (n = 52; 11.5%), sepsis (n = 10; 2.2%), and septic shock (n = 6; 1.3%). Of those, UAS was not used in 29 (55.8%), 7 (70%), and 5 (83.3%) cases, respectively (all p > 0.05). At multivariable logistic regression analysis, performing URS without UAS was not associated with the risk of having fever and sepsis, but it increased the risk of septic shock (OR = 14.6; 95% CI = 1.08-197.1). Moreover, age-adjusted CCI score (for fever-OR = 1.23; 95% CI = 1.07-1.42, sepsis-OR = 1.47; 95% CI = 1.09-1.99, and septic shock-OR = 1.61; 95% CI = 1.08-2.42, respectively), history of fever secondary to stones (for fever-OR = 2.23; 95% CI = 1.02-4.90) and preoperative positive urine culture (for sepsis-OR = 4.87; 95% CI = 1.12-21.25) did emerge as further associated risk factors. The use of UAS emerged to prevent the onset of septic shock in patients treated with URS, with no clear benefit in terms of fever and sepsis. Further studies may help clarify whether the reduction in fluid reabsorption load mediated by UAS is protective against life-threatening conditions in case of infectious complications. The patients' baseline characteristics remain the main predictors of infectious sequelae in a clinical setting.

Clinical Analysis of Pediatric Acute Leukemia Complicated with Septic Shock

To analyze the clinical characteristics of predictors in pediatric acute leukemia complicated with septic shock and explore the prognostic factors. The clinical characteristics of 70 children with acute leukemia and complicated with septic shock hospitalized in Sun Yat-sen Memorial Hospital from March 2012 to March 2021 were retrospectively analyzed. The clinical characteristics of patients in survival group and death group were analyzed and compared. Multiple logistic regression was used to test for predictors of death. Among the 70 children, 41 were males and 29 were females, with a median age of 7.0 (1.0-15.0) years old. 81.4% were hospital acquired infections. The pathogens were mostly Gram-negative bacteria (50/66, 75.8%) and the clinical manifestations were cold shock. Mortality rate was 34.3% (24/70). The length of hospitalization, duration of fever and antibiotic exposure longevity before the onset of septic shock were significantly different between survival group and death group. At septic shock onset, compared with the survival group, patients in the death group were younger, had lower platelet counts and higher levels of C-reactive protein and procalcitonin, and were more likely to have acute heart failure and more mechanical ventilation (all p<0.05). The results of multivariable analysis showed that mortality was independently associated with pediatric sequential organ failure assessment score (pSOFA) (odds ratio: 1.616, 95% CI: 1.160-2.251, p=0.005) and acute heart failure (odds ratio: 18.308, 95% CI: 1.939-172.911, p=0.011). In addition, the ROC curve analysis showed that pSOFA score had AUC of 0.8551 (95% CI: 0.7607-0.9495, p<0.001) predicting PICU mortality and its best predictive value was >9.5 (sensitivity 75.0%, specificity 87.0%). Pediatric acute leukemia complicated with septic shock is characterized as rapid deterioration and high mortality. A pSOFA score greater than 9.5 and acute heart failure are associated with poor outcomes.

The Role of Left Ventricular Ejection Fraction and Left Ventricular Outflow Tract Velocity-Time Integral in Assessing Cardiovascular Impairment in Septic Shock.

Background: the role of echocardiography in septic shock remains controversial, since depressed cardiac afterload may overestimate left ventricular (LV) systolic performance and mask septic cardiomyopathy (SC). We hypothesized that afterload-adjusted LV ejection fraction (LVEF) and LV outflow tract velocity-time integral (VTI) values for given systemic vascular resistances (SVR) could provide novel insights into recognizing and stratifying the severity of SC. Methods: in this observational, monocentric study, we prospectively included 14 mechanically-ventilated patients under septic-shock who all had a Pulse index Continuous Cardiac Output (PiCCO) system in place for hemodynamic monitoring. Echocardiographic and PiCCO longitudinal examinations (71 measurements overall) were performed simultaneously at the onset of septic shock and every 12 h for 60 h overall. Results: VTI-derived stroke volume (SV) and cardiac output (CO) were significantly correlated with PiCCO measurements (r ≥ 0.993, both p < 0.001). LVEF and VTI showed linear and exponential inverse correlation to SVR (R2 = 0.183 vs. 0.507 and p < 0.001 vs. p < 0.001, respectively). The equations LVEF = 86.168 − 0.011 × SVR and VTI = 41.23 × e(−0.0005×SVR) were found to provide “predicted” values for given SVR. Measured to predicted LVEF ratios (for given SVR), the afterload-adjusted LVEF defined the severity of SC (mild ≥ 90%, 80% ≤ moderate < 90% and severe < 80%). Mild SC demonstrated normal/supra-normal LVEF, normal VTI and SVR. Moderate SC showed lower LVEF and SVR, yet increased LV end-diastolic volume (LVEDV), VTI, SV and CO compared with mild SC (all p < 0.05). Severe SC was distinguished from moderate SC by markedly reduced LVEF, LVEDV, VTI, SV, CO and significantly increased SVR (all p < 0.05). LVEF and VTI decreased over time in mild SC, LVEF decreased in moderate SC, and LVEF and VTI increased over time in severe SC (p ≤ 0.038). LVEF and VTI demonstrated significant performance in identifying severe SC [cut-off < 61.5%, area under the curve (AUC) = 1 ± 0.0, sensitivity/specificity = 100/100, p < 0.001 vs. cut-off < 17.9 cm, AUC = 0.882 ± 0.042, sensitivity/specificity = 80/77, p < 0.001, respectively]. VTI but not LVEF demonstrated significant diagnostic performance in identifying both SVR < 800 dynes·s·cm−5 and SVR > 1500 dynes·s·cm−5 (cut-off > 24.46 cm, AUC = 0.889 ± 0.049, sensitivity/specificity = 75/100, p < 0.001; cut-off < 16.8, AUC = 0.0.857 ± 0.082, sensitivity/specificity = 83/86, p = 0.002, respectively).Conclusions: our study suggests that ICU bedside echocardiographic assessment of LVEF, VTI and their adjusted to corresponding SVR values provides valuable insights for the comprehension of SC phenotypes, underlying vasoplegia and cardiac output fluctuations in septic shock.

Cardiac and vascular effects of low-dose steroids during the early phase of septic shock: An echocardiographic study.

BackgroundLow-dose steroids are known to increase arterial pressure during septic shock through restoration of vasopressor response to norepinephrine. However, their effects on cardiac performance and ventriculo-arterial coupling (VAC) have never been scrutinized during human septic shock. The aim of this study was to perform a comprehensive description of the cardiovascular effects of low-dose steroids using modern echocardiographic tools (including speckle tracking imaging).MethodsThis prospective study was conducted in the intensive care unit (ICU) of a university hospital in France. Consecutive adult patients admitted for septic shock and requiring low-dose steroid therapy were prospectively enrolled within 24 h of septic shock onset. We recorded hemodynamic and echocardiographic data to explore left ventricle (LV) contractility, loading conditions and VAC just before the initiation of low-dose steroids (50 mg intravenous hydrocortisone plus 50 μg enteral fludrocortisone) and 2–4 h after.ResultsFifty patients [65 (55–73) years; 33 men] were enrolled. Arterial pressure, heart rate, almost all LV afterload parameters, and most cardiac contractility parameters significantly improved after steroids. VAC improved with steroid therapy and less patients had uncoupled VAC (> 1.36) after (24%) than before (44%) treatment.ConclusionIn this comprehensive echocardiographic study, we confirmed an improvement of LV afterload after initiation of low-dose steroids. We also observed an increase in LV contractility with improved cardiovascular efficiency (less uncoupling with decreased VAC).

Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock

BackgroundAngiotensin II is one of the vasopressors available for use in septic shock. However, its effects on the septic myocardium remain unclear. The aim of the study was to compare the effects of angiotensin II and norepinephrine on cardiac function and myocardial oxygen consumption, inflammation and injury in experimental septic shock.MethodsThis randomized, open-label, controlled study was performed in 20 anesthetized and mechanically ventilated pigs. Septic shock was induced by fecal peritonitis in 16 animals, and four pigs served as shams. Resuscitation with fluids, antimicrobial therapy and abdominal drainage was initiated one hour after the onset of septic shock. Septic pigs were randomly allocated to receive one of the two drugs to maintain mean arterial pressure between 65 and 75 mmHg for 8 h.ResultsThere were no differences in MAP, cardiac output, heart rate, fluid balance or tissue perfusion indices in the two treatment groups but myocardial oxygen consumption was greater in the norepinephrine-treated animals. Myocardial mRNA expression of interleukin-6, interleukin-6 receptor, interleukin-1 alpha, and interleukin-1 beta was higher in the norepinephrine than in the angiotensin II group.ConclusionsIn septic shock, angiotensin II administration is associated with a similar level of cardiovascular resuscitation and less myocardial oxygen consumption, and inflammation compared to norepinephrine.

TIME FROM HOSPITAL ADMISSION TO ONSET OF SEPTIC SHOCK IS ASSOCIATED WITH HIGHER IN-HOSPITAL MORTALITY.

Objective: Several studies have shown septic shock developing later during the hospital stay is associated with higher mortality. However, the precise point at which time from hospital admission to the onset of septic shock (admission-shock-onset-time) becomes an independent prognostic marker of mortality remains unknown. This study evaluated the association between admission-shock-onset-time and in-hospital mortality among patients with septic shock and the optimal cutoff period to categorize early- and late-onset septic shock. Method: We conducted a single-center retrospective, observational cohort study at a quaternary academic hospital comprising adult patients with septic shock admitted to a medical intensive care unit (ICU) from January 2011 to December 2020. A multivariable additive logistic regression model was developed to assess if log-transformed admission-shock-onset-time was associated with in-hospital mortality. The thin plate spline function was used to describe the nonlinear relationship between the log-transformed admission-shock-onset-time and in-hospital mortality. The primary outcome was in-hospital mortality, and the secondary outcome was ICU mortality. Results: Two thousand five hundred twenty patients met the inclusion criteria with an overall in-hospital mortality of 37.3%. The log-transformed admission-shock-onset-time was associated with higher in-hospital and ICU mortality even after adjusting for clinical variables. The odds ratio for in-hospital mortality continued to increase throughout the observation period. The adjusted odds ratio exceeded 2 in between 20.1 and 54.6 h, and it surpassed 3 in between 54.6 and 148.4 h of the time from the hospital admission to shock onset. Conclusion: In-hospital mortality continued to rise as admission-shock-onset-time increased in patients with septic shock. No clear dichotomization between early and late septic shock could be ascertained, and this categorization may limit our understanding of the temporal relationship of shock onset to mortality.

The Relationship Between Norepinephrine Equivalent Dose of Vasopressors Within 24 Hours From the Onset of Septic Shock and In-Hospital Mortality Rate

The reported mortality rate of septic shock is 30% to 40%.1 However, these reported mortality rates do not take into consideration the severity of septic shock. There remains limited evidence on the prognosis of patients with septic shock whose condition requires higher doses of vasopressors. Although it is commonly perceived that higher doses of vasopressors translate into worsened clinical outcomes, the complex relationship between vasopressor dose and death has not been well-described. Therefore, we investigated the relationship between cumulative vasopressor dosage and in-hospital mortality rates in patients with septic shock.

Plasma Transfusion in Septic Shock-A Secondary Analysis of a Retrospective Single-Center Cohort.

In sepsis, both beneficial and detrimental effects of fresh frozen plasma (FFP) transfusion have been reported. The aim of this study was to analyze the indication for and effect of FFP transfusion in patients with septic shock. We performed a secondary analysis of a retrospective single-center cohort of all patients treated for septic shock at the interdisciplinary surgical intensive care unit (ICU) of the Heidelberg University Hospital. Septic shock was defined according to sepsis-3 criteria. To assess the effects of FFP administration in the early phase of septic shock, we compared patients with and without FFP transfusion during the first 48 h of septic shock. Patients who died during the first 48 h of septic shock were excluded from the analysis. Primary endpoints were 30- and 90-day mortality. A total of 261 patients were identified, of which 100 (38.3%) received FFP transfusion within the first 48 h after septic shock onset. The unmatched analysis showed a trend toward higher 30- and 90-d mortality in the FFP group (30 d: +7% p = 0.261; 90 d: +11.9% p = 0.061). In the propensity-matched analysis, 30- and 90-day mortality were similar between groups. Plasma administration did not influence fluid or vasopressor need, lactate levels, ICU stay, or days on a ventilator. We found no significant harm or associated benefit of FFP use in the early phase of septic shock. Finally, plasma should only be used in patients with a strong indication according to current recommendations, as a conclusive evaluation of the risk-benefit ratio for plasma transfusion in septic shock cannot be made based on the current data.

P8 TRANSVENOUS LEAD EXTRACTION AS LIFE–SAVING PROCEDURE IN SEPTIC SHOCK

Abstract Introduction With the increase of implant centers and the related procedures also increased the complications associated with the pacemakers and defibrillators implant. Transvenous lead extraction, saving procedure in presence of sepsis or septic shock, is the best therapy for leads’ infections because medical treatment alone is not effective to eradicating the infection. Materials and Methods In May 2021 was sent to our O.U. from the ER a 61–year–old patient for symptomatic Afib with rapid ventricular response. In 2014 the patient received an ICD implantation for obstructive hypertrophic cardiomyopathy, later found to be an amyloidosic infiltrative cardiomyopathy. The TEE reported EF 30%, thrombus filling left and right atrial appendage and vegetations all over the lead. Despite the patient was apyretic, laboratory tests showed neutrophilic leukocytosis and an increase in inflammation indices. The series of blood cultures were instead negative. However, for the occurrence of septic state, has been set up an antibiotic therapy and DOACs therapy on the advice of an infectious disease specialist. PET TAC confirmed an infection along leads. For a progressive clinical improvement, the patient started a cardiological rehabilitation cycle. Six days later, due to the onset of hyperpyressia and septic shock, the patient was intubated bacause of an acute respiratory failure and transferred urgently in intensive care. For the onset of MOF by sepsis on an endocarditic basis, has been indicated an extraction procedure. Results After performing the extraction procedure, it was found an immediate improvement of both the clinical conditions and laboratory parameters. In fact the next day it was possible to proceed to the extubation. Laboratory tests showed a progressive normalization of inflammation and leukocytosis indices; TEE confirmed the absence of vegetations and thrombotic material in the atrial appendage. The patient, apyretic, was sent to cardiological rehabilitation to complete the antibiotic–therapy cycle and, subsequently, at home with Life Vest. After cardiological revaluation and in absence of sepsis signs, the patient was re–implanted with a contralateral ICD. Conclusions In accordance with guidelines and literature, transvenous leads extraction constitutes, despite the potential risks associated with the procedure, the true resolutive therapy in device infections.