Early peripheral perfusion monitoring in septic shock.

Septic shock is a frequent critical clinical condition and a leading cause of death in critically ill individuals. However, it is challenging to identify affected patients early. In this article, we discuss new perspectives on the methods and uses of peripheral perfusion monitoring, considering the concept of a dysregulated response. Physical examination, and visual and ultrasonographic techniques are used to measure peripheral microcirculatory blood flow to reflect tissue perfusion. Compared with other monitoring techniques, peripheral perfusion monitoring has the benefits of low invasiveness and good repeatability, and allows for quick therapeutic judgments, which have significant practical relevance. Peripheral perfusion monitoring is an effective tool to detect early signs of septic shock, autonomic dysfunction, and organ damage. This method can also be used to evaluate treatment effectiveness, direct fluid resuscitation and the use of vasoactive medications, and monitor vascular reactivity, microcirculatory disorders, and endothelial cell damage. Recent introductions of novel peripheral perfusion monitoring methods, new knowledge of peripheral perfusion kinetics, and multimodal peripheral perfusion evaluation methods have occurred. To investigate new knowledge and therapeutic implications, we examined the methodological attributes and mechanisms of peripheral perfusion monitoring, in this study.

The iNKT cell ligand α-GalCer prevents murine septic shock by inducing IL10-producing iNKT and B cells.

Introduction: α-galactosylceramide (α-GalCer), a prototypical agonist of invariant natural killer T (iNKT) cells, stimulates iNKT cells to produce various cytokines such as IFNγ and IL4. Moreover, repeated α-GalCer treatment can cause protective or pathogenic outcomes in various immune-mediated diseases. However, the precise role of α-GalCer-activated iNKT cells in sepsis development remains unclear. To address this issue, we employed a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced murine sepsis model and two alternative models. Methods: Sepsis was induced in wild-type (WT) C57BL/6 (B6) mice by three methods (LPS/D-GalN, α-GalCer/D-GalN, and cecal slurry), and these mice were monitored for survival rates. WT B6 mice were intraperitoneally injected with α-GalCer or OCH (an IL4-biased α-GalCer analog) one week prior to the induction of sepsis. To investigate the effects of α-GalCer-mediated iNKT cell activation on sepsis development, immune responses were analyzed by flow cytometry using splenocytes and liver-infiltrating leukocytes. In addition, a STAT6 inhibitor (AS1517499) and an IL10 inhibitor (AS101) were employed to evaluate the involvement of IL4 or IL10 signaling. Furthermore, we performed B cell adoptive transfers to examine the contribution of α-GalCer-induced regulatory B (Breg) cell populations in sepsis protection. Results: In vivo α-GalCer pretreatment polarized iNKT cells towards IL4- and IL10-producing phenotypes, significantly attenuating LPS/D-GalN-induced septic lethality in WT B6 mice. Furthermore, α-GalCer pretreatment reduced the infiltration of immune cells to the liver and attenuated pro-inflammatory cytokine production. Treatment with a STAT6 inhibitor was unable to modulate disease progression, indicating that IL4 signaling did not significantly affect iNKT cell-mediated protection against sepsis. This finding was confirmed by pretreatment with OCH, which did not alter sepsis outcomes. However, interestingly, prophylactic effects of α-GalCer on sepsis were significantly suppressed by treatment with an IL10 antagonist, suggesting induction of IL10-dependent anti-inflammatory responses. In addition to IL10-producing iNKT cells, IL10-producing B cell populations were significantly increased after α-GalCer pretreatment. Conclusion: Overall, our results identify α-GalCer-mediated induction of IL10 by iNKT and B cells as a promising option for controlling the pathogenesis of postoperative sepsis.

Bioimpedance analysis for fluid status assessment in critically ill septic patients.

AIM: The aim of this study was to assess the usefulness of bioimpedance analysis in fluid status evaluation in patients with sepsis and septic shock admitted to the adult ICU.

Association between heart rate and mortality in patients with septic shock: an analysis revealed by time series data.

BACKGROUND: Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. METHODS: This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. RESULTS: A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P < 0.001, non-linear P < 0.001) when TWA-HR > 85 beats per minute (bpm). The log-rank test revealed in terms of the 28-day mortality, the hazard ratio (HR) (95% confidence interval [CI]) was 1.92 (1.78-2.06, P < 0.001) for patients with high TWA-HR compared to normal TWA-HR group. Similarly, for the ICU mortality, the HR (95% CI) was 1.64 (1.52-1.78, P < 0.001), and for the in-hospital mortality, the HR (95% CI) was 1.61 (1.48-1.76, P < 0.001). Collectively, the sensitivity analysis consistently demonstrated higher 28-day mortality, ICU mortality, and in-hospital mortality in patients with TWA-HR > 85 bpm. CONCLUSION: Patients with septic shock whose heart rate was controlled no more than 85 bpm during ICU stay received survival benefit in terms of 28-day, ICU and in-hospital mortality. .

Clinical and epidemiological factors related to mortality due to septic shock in a pediatric intensive care unit.

INTRODUCTION: Septic shock is a potentially life-threatening condition. The aim of this study was to identify clinical and epidemiological factors associated with mortality in pediatric patients admitted to a pediatric intensive care unit (PICU) with septic shock. MATERIALS AND METHODS: A retrospective comparative case series study was conducted with children aged 1 month to 14 years with septic shock from 2018 to 2020 in a PICU in Lima, Peru. Patients were divided into deceased and survivor groups based on their condition at discharge from the PICU. The influence of each variable on mortality was assessed using a logistic regression model. RESULTS: A total of 174 patients were included in the study, with 51 (29.3%) fatalities. Deceased patients, compared to survivors, were older, had a higher incidence of oncological disease (31.4% vs. 14.6%; p = 0.011), more frequently presented with hemoglobin ≤ 9 g/dL (44% vs. 28%; p = 0.043), lactate > 2 mmol/L (70% vs. 44%; p = 0.002), platelets ≤ 150 (×103)/µL (77% vs. 42%; p < 0.001), and pH ≤ 7.1 (31% vs. 6%; p < 0.001). In the logistic regression model, factors related to mortality were having a pH ≤ 7.1 (odds ratio [OR] = 8.95; 95% confidence interval [CI]: 2.52-31.75) and platelets ≤ 150 (×103)/µL (OR = 3.89; 95% CI: 1.40-10.84). CONCLUSIONS: Factors associated with mortality in pediatric patients with septic shock were a pH ≤ 7.1 and platelets ≤ 150 (×103)/µL in the assessments conducted upon admission to the PICU.

INTRODUCCIÓN: El shock séptico es una condición potencialmente mortal. El objetivo del estudio fue identificar factores clínicos y epidemiológicos relacionados con la mortalidad en pacientes que ingresaron por shock séptico a una Unidad de Cuidados Intensivos Pediátricos (UCIP). MÉTODOS: Estudio retrospectivo tipo serie de casos comparativos con niños de 1 mes a 14 años hospitalizados por shock séptico del 2018 al 2020 en una UCIP de Lima en Perú. Los pacientes fueron divididos en fallecidos y vivos según su condición al alta de la Unidad. La influencia de cada variable sobre la mortalidad fue evaluada mediante un modelo de regresión logística. RESULTADOS: Ingresaron 174 pacientes al estudio, fallecieron 51 (29.3%). Los fallecidos en comparación con los vivos fueron de mayor edad, tuvieron más casos oncológicos (31.4% vs. 14.6%; p = 0.011), presentaron con mayor frecuencia hemoglobina ≤ 9 g/dL (44% vs. 28%; p = 0.043), lactato > 2 mmol/L (70% vs. 44%; p = 0.002), plaquetas ≤ 150 (×103)/µL (77% vs. 42%; p < 0.001) y pH ≤ 7,1 (31% vs. 6%; p < 0.001). En la regresión logística ajustada los factores que se relacionaron con la mortalidad fueron tener un pH ≤ 7,1 (OR = 8.95; IC 95%: 2.52 a 31.75) y plaquetas ≤ 150 (×103)/µL (OR = 3.89; IC 95%: 1.40 a 10.84). CONCLUSIONES: Los factores relacionados con la mortalidad en pacientes hospitalizados por shock séptico fueron tener un pH ≤ 7.1 y plaquetas ≤ 150 (×103)/µL en los controles realizados al ingreso de la UCIP.

Role of arterial blood glucose and interstitial fluid glucose difference in evaluating microcirculation and clinical prognosis of patients with septic shock: a prospective observational study.

BACKGROUND: Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA-I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock. METHODS: The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA-I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA-I interval was analyzed. RESULTS: A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6-16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9-40), of whom 18 died during ICU stay. The GA-I levels were negative correlation with CRT (r = 0.369, P < 0.001), Lac (r = -0.269, P < 0.001), skin mottling score (r=-0.223, P < 0.001), and were positively associated with urine volume (r = 0.135, P < 0.05). The ICU mortality rate of patients with septic shock presenting GA-I ≤ 0.30 mmol/L and ≥ 2.14 mmol/L was significantly higher than that of patients with GA-I at 0.30-2.14 mmol/L [65.2% vs. 15.0%, odds ratio (OR) = 10.625, 95% confidence interval (CI): 2.355-47.503]. CONCLUSION: GA-I was correlated with microcirculation parameters, and with differences in survival. Future studies are needed to further explore the potential impact of GA-I on microcirculation and clinical prognosis of septic shock, and the bedside monitoring of GA-I may be beneficial for clinicians to identify high-risk patients.

Prognostic risk factors for pyogenic liver abscess caused by Klebsiella pneumoniae.

BACKGROUND: Pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae can vary in severity, and several risk factors for the development of organ dysfunction in PLA have been implicated. However, few studies to date have explored the most common risk factors for clinical severity. METHODS: We conducted a study on patients with PLA caused by Klebsiella pneumoniae between February 2013 and December 2022.Using logistic regression analysis, we sought to identify factors associated with positive blood culture, septic shock, and intensive care unit (ICU) admission. RESULTS: After included 200 patients, we found that an elevated procalcitonin (PCT) level (p = 0.03), higher glucose level (p = 0.03), and lower total cholesterol (TC) level (p = 0.01) were associated with a higher likelihood of positive blood bacteriological culture. Additionally, an increased PCT level (p = 0.02) and lower TC level (p < 0.01) were associated with an elevated risk of septic shock. Furthermore, a higher PCT level (p < 0.01) was associated with a higher probability of ICU admission. CONCLUSION: In patients with PLA caused by Klebsiella pneumoniae, the PCT, glucose, and TC levels were found to be associated with positive blood culture, septic shock, and ICU admission.

Necrotizing Fasciitis Caused by Group A Streptococcus.

BACKGROUND: Group A Streptococcus causes a variety of human infections, including the life-threatening necrotizing fasciitis, which may be ignored by the patient. From hours to days, the infection may progress from an apparently benign skin lesion, usually mistaken for a spider or insect bite, to a highly lethal disease. We present a case of 57-year-old male with skin lesions on swelling left upper limb. METHODS AND RESULTS: The culture of secretion from epidermis and blood were positive for Group A Streptococcus (GAS), type ß hemolytic streptococcus. Intensive anti-infection therapy was applied. However, the necrosis of the limb deteriorated rapidly. He died from multiple organ failure, streptococcal toxic shock syndrome (STSS) and disseminated intravascular coagulation 13 days later. CONCLUSIONS: Necrotizing fasciitis is a rapidly progressive, destructive bacterial infection. Early recognition is the most important factor for survival.

Rhabdomyolysis presenting with septic shock in a 21 year old female patient: A case report.

Rhabdomyolysis is a clinical condition characterized by the release of intracellular content into the bloodstream, resulting in the breakdown of skeletal muscle. The released intracellular content includes electrolytes, enzymes, and myoglobin, leading to systemic complications. The clinical presentation may vary, ranging from an asymptomatic increase in serum levels of enzymes released from damaged muscles to worrisome conditions such as volume depletion, metabolic and electrolyte abnormalities, and acute kidney injury. The diagnosis is confirmed when the serum creatine kinase (CK) level is > 1000 U/L or at least 5x the upper limit of normal. In this study, we aimed to evaluate a 21-year-old female patient presenting with nontraumatic exercise-unrelated rhabdomyolysis, accompanied by acute renal failure and septic shock.

Calcification following tongue necrosis induced by vasopressor use in a nonintubated patient with septic shock: a case report.

BACKGROUND: Tongue necrosis is a rare and relatively uncommon condition, usually caused by vasculitis, thrombosis, severe hypotension due to septic or cardiogenic shock, vasopressor use, or intubation. Following damage such as necrosis, dystrophic calcification, a type of soft tissue calcification, can occur. CASE PRESENTATION: Herein, we present a unique case of bilateral tongue necrosis in a patient with nonintubated septic shock. A 70-year-old East Asian man with no significant medical history presented to the emergency department with postprandial epigastric pain. The patient was admitted to the intensive care unit with hypotension due to septic shock and disseminated intravascular coagulation. After a short course of vasopressors, the patient developed tongue discoloration and swelling without limb ischemia. Computed tomography was performed to observe the tongue necrosis, and calcification of the tongue was found. The patient was successfully treated by wiping the area with a hexamidine-soaked gauze. CONCLUSION: Tongue necrosis remains a rare finding, and its occurrence as a complication of vasopressor use is even rarer. Therefore, even with relatively short courses of vasopressors in the intensive care unit, daily visualization of the tongue to check for discoloration, along with daily inspection and pulse checks of the limbs, can help identify vasospasms. These measures allow for prompt intervention, minimizing permanent damage and shortening the recovery time.

[Group A-streptococcal infection during pregnancy]. / Groep A-streptokokkeninfectie tijdens de zwangerschap.

Group A-streptococcal (GAS) infection can lead to various clinical presentations and is fulminant when it reaches the deep tissues, leading to a high morbidity and mortality. The severity of postpartum GAS infections is widely known. In this case report we describe the course of disease in a pregnant patient with GAS toxic shock syndrome with initial complaints of abdominal pain, diarrhea and fetal demise at first presentation. Within 10 hours this patient died. It is important to stay vigilant for a fulminant GAS infection in pregnant patients, to recognize it quickly and treat it adequately.

[Extracorporeal procedures in sepsis]. / Extrakorporale Verfahren bei der Sepsis.

Sepsis and septic shock are frequent and severe clinical pictures in intensive care medicine that result from a dysregulated immune response to an infection and cause a high mortality rate. This article provides an overview of the various extracorporeal procedures used to treat sepsis. Various procedures are used to treat sepsis and septic shock. These include high-volume hemofiltration (HVHF), very high-volume hemofiltration (VHVHF), high cut-off filter (HCO), polymyxin B hemoperfusion and cytokine adsorption filters. The HVHF and VHVHF remove inflammatory mediators but show no significant benefit in terms of stabilization and survival in sepsis patients. The HCO filters effectively eliminate cytokines but so far there is no evidence of a survival benefit. Polymyxin B hemoperfusion shows promising results in initial studies in certain patient groups, while evidence for cytokine adsorption filters is limited. Combined plasma filtration and adsorption (CPFA) and therapeutic plasma exchange (TPE) have so far shown promising results in small studies. Although CPFA shows no survival benefit, TPE may have protective effects on the vascular glycocalyx. Extracorporeal procedures carry risks such as thrombosis and loss of proteins and clotting factors. The therapeutic benefit of these procedures in the treatment of sepsis remains unclear and further prospective randomized multicenter studies are needed to evaluate their efficacy and safety. There are currently no guideline recommendations for the routine use of these procedures in sepsis.

Evaluation of Amiodarone Administration in Patients with New-Onset Atrial Fibrillation in Septic Shock.

Background and Objective: New-onset atrial fibrillation (NOAF) is a common cardiac condition often observed in intensive care units. When amiodarone is used to treat this condition, either to maintain sinus rhythm after electrical cardioversion or to control heart rate, complications can arise when a systemic pathology is present. Systemic pathology can result in a decrease in cardiac output and blood pressure, making the management of NOAF and septic shock challenging. Limited international research exists on the coexistence of NOAF and septic shock, making it difficult to determine the optimal course of treatment. While amiodarone is not the primary choice of antiarrhythmic drug for patients in septic shock, it may be considered for those with underlying cardiac issues. This paper aims to investigate the safety of administering amiodarone to patients with septic shock and explore whether another antiarrhythmic drug may be more effective, especially considering the cardiac conditions that patients may have. Materials and Methods: To write this article, we searched electronic databases for studies where authors used amiodarone and other medications for heart rate control or sinus rhythm restoration. Results: The studies reviewed in this work have shown that for the patients with septic shock and NOAF along with a pre-existing cardiac condition like a dilated left atrium, the use of amiodarone may provide greater benefits compared to other antiarrhythmic drugs. For patients with NOAF and septic shock without underlying heart disease, the initial use of propafenone has been found to be advantageous. However, a challenge arises when deciding between rhythm or heart rate control using various drug classes. Unfortunately, there is limited literature available on this specific scenario. Conclusions: NOAF is a frequent and potentially life-threatening complication occurring in one out of seven patients with sepsis, and its incidence is rising among patients with septic shock.

Association between the lactate-albumin ratio and microcirculation changes in Pediatric Septic patients.

A lactate/albumin ratio (LAR) greater than 0.5 measured early in the course of pediatric critical illness is associated with greater mortality. Whether the elevated LAR can be explained by microcirculation disorders in children with sepsis is not known. In this longitudinal retrospective study (January 2021-January 2024), serum albumin and lactate were measured on admission to the pediatric intensive care unit (PICU), with sublingual video microscopy performed simultaneously to measure microcirculation. A total of 178 children were included, 37% of whom had septic shock measured with the Phoenix Sepsis Score. Patients with remote sepsis had greater odds of an elevated LAR (aOR 6.87: 95% CI 1.98-23.73; p < 0.01). Children with an elevated LAR had more microvascular blood flow abnormalities (aOR 1.31 95% CI 1.08-1.58; p < 0.01), lower 4-6-micron capillary density (aOR 1.03 95% CI 1.01-1.05; p < 0.01) and greater odds of dying (aOR 3.55 95% CI 1.21-10.38; p = 0.02) compared to those with a low LAR. We found no association between LAR and endothelial glycocalyx degradation. A normal LAR is associated with less risk of microcirculatory injury (aOR 0.77 95% CI 0.65-0.93; p < 0.01). In children with sepsis, an elevated LAR is associated with microcirculation abnormalities (microvascular density and flow). The lactate/albumin ratio is a potentially useful biomarker for microcirculatory injury in sepsis.

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.

INTRODUCTION: Sepsis 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). METHODS: We 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. RESULTS: Systolic 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. CONCLUSION: SBP, 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.

In sepsis or septic shock, prolonged vs. intermittent infusion of ß-lactam antibiotics reduces mortality at 90 d.

SOURCE CITATION: Abdul-Aziz MH, Hammond NE, Brett SJ, et al. Prolonged vs intermittent infusions of ß-lactam antibiotics in adults with sepsis or septic shock: a systematic review and meta-analysis. JAMA. 12 June 2024. [Epub ahead of print.] 38864162.

Effect of timing of intubation on clinical outcomes of patients with septic shock: a retrospective cohort study.

Evidence-based data regarding the timing of the application of invasive mechanical ventilation among adults with septic shock is insufficient. The guidelines fail to provide clear advice about the optimal time to initiate this support. Consequently, we aimed to investigate whether early intubation could improve survival rates in septic shock patients. We conducted a retrospective analysis of the MIMIC-IV database to evaluate the effectiveness of early intubation on mortality in a cohort of septic shock patients. Adults diagnosed with septic shock, according to the Sepsis-3 definition, were included. They were categorized into an early intubation group (first 8 h after vasopressor initiation) and a non-early intubation group (unexposed). A propensity score matching (PSM) analysis was used to balance the baseline characteristics between the two groups. The primary outcomes were 30-day and 90-day all-cause mortality rates. In addition, we employed the restricted cubic spline to analyze the potential non-linear relationship between the timing of intubation and 30-day or 90-day all-cause mortality. A total of 6864 adult patients, of whom 2048 were intubated in the first 8 h, were evaluated in the final cohort. Following a 1:1 PSM procedure, 2786 patients were successfully paired. At 30 days, 288 of 1393 patients (20.7%) in the early intubation group and 381 of 1393 patients (27.4%) in the non-early intubation group had died (hazard ratio [HR] 0.717; 95% confidence interval [CI] 0.616-0.836; p < 0.001). Similarly, the results also showed that early intubation was associated with a lower 90 day all-cause mortality rate (HR 0.761; 95% CI 0.663-0.874; p < 0.001). Furthermore, ICU and hospital lengths of stay were significantly different between the groups (3.6 [1.9, 7.1] vs. 2.3 [1.3, 4.3]; p < 0.001 and 8.9 [5.4, 15.1] vs. 7.2 [4.5, 12.0]; p < 0.001). In the subgroup analysis, we further confirmed the robustness of our findings. Additionally, we found that the timing of intubation is inversely U-shaped correlated to the 30 day all-cause mortality rate. Among adult patients with septic shock, the early initiation of invasive mechanical ventilation could improve clinical outcomes. The timing of intubation demonstrated an inverse U-shaped association with the 30 day all-cause mortality rate, with the peak risk of death occurring at 50.5 h after septic shock.

Landiolol for heart rate control in patients with septic shock and persistent tachycardia. A multicenter randomized clinical trial (Landi-SEP).

PURPOSE: Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting ß1-blocker landiolol. METHODS: This randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80-94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events. RESULTS: Out of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4-28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events. CONCLUSION: The ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control.