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Background: This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock. Methods: Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L). Results: Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08–3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01–6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79–37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54–30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019). Conclusion: In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency. [ABSTRACT FROM AUTHOR]

Background: Intravenous (IV) vasopressors are the mainstay of physiological support for hemodynamically unstable patients. However, the role of oral vasopressors remains unclear. The objective of our study was to evaluate the feasibility of evaluating midodrine for critically ill patients with IV vasopressor-dependent shock. Methods: We conducted a single-center, concealed-allocation, parallel-group, blinded feasibility randomized controlled trial (RCT) evaluating the effect of oral midodrine versus placebo on IV vasopressor-dependent shock in the intensive care unit (ICU). The study was performed in a medical-surgical ICU at the University of Alberta Hospital from April 2021 to July 2022. We included patients aged 18 years or older admitted to the ICU with ongoing vasopressor support with decreasing vasopressor dose(s). Patients were randomly assigned 1:1 to midodrine or a placebo for the duration of their IV vasopressor therapy. The primary outcome was study feasibility and secondary outcomes included patient-centered outcomes. Feasibility was assessed through rate of recruitment, adherence to study protocol, and patient safety. Results: Twenty patients were enrolled in the study and underwent randomization (n = 11 midodrine, n = 9 control). Recruitment was recorded at 1.2 participants per month, protocol adherence was 90%, and allocation remained concealed. No adverse events were reported in either group. Sepsis was the most common cause of shock in both groups. The midodrine group had a shorter length of ICU stay of 9.6 (SD 8.7) vs 10.4 (SD 14.5) days. Hospital mortality was lower for the midodrine group (n = 2, 18.2% vs n = 4, 37.5%). Vasopressor re-initiation after 24 h was more frequent in the midodrine group (n = 4, 36.4% vs n = 2, 25%). There were no readmissions to the ICU following discharge in either group. Conclusions: The evaluation of midodrine for patients in the ICU is feasible and safe. This trial will inform future large-scale RCTs regarding the utility of midodrine in critically ill patients with IV vasopressor-dependent shock. Trial registration: This pilot RCT was registered at clinicaltrials.gov (NCT04489589). Registered July 27, 2020. https://clinicaltrials.gov/study/NCT04489589 [ABSTRACT FROM AUTHOR]

Background: Sepsis is a condition with high mortality and morbidity, characterized by deregulation of the immune response against the pathogen. Current treatment strategies rely mainly on antibiotics and supportive care. However, there is growing interest in exploring cell-based therapies as complementary approaches. Human liver stem cells (HLSCs) are pluripotent cells of mesenchymal origin, showing some advantages compared to mesenchymal stem cells in terms of immunomodulatory properties. HSLC-derived extracellular vesicles (EVs) exhibited a superior efficacy profile compared to cells due to their potential to get through biological barriers and possibly to avoid tumorigenicity and showed to be effective in vivo and ex vivo models of liver and kidney disease. The potential of HLSCs and their EVs in recovering damage to distal organs due to sepsis other than the kidney remains unknown. This study aimed to investigate the therapeutic potential of the intravenous administration of HSLCs or HSLCs-derived EVs in a murine model of sepsis. Results: Sepsis was induced by caecal ligation and puncture (CLP) on C57/BL6 mice. After CLP, mice were assigned to receive either normal saline, HLSCs or their EVs and compared to a sham group which underwent only laparotomy. Survival, persistence of bacteraemia, lung function evaluation, histology and bone marrow analysis were performed. Administration of HLSCs or HLSC-EVs resulted in improved bacterial clearance and lung function in terms of lung elastance and oedema. Naïve murine hematopoietic progenitors in bone marrow were enhanced after treatment as well. Administration of HLSCs and HLSC-EVs after CLP to significantly improved survival. Conclusions: Treatment with HLSCs or HLSC-derived EVs was effective in improving acute lung injury, dysmyelopoiesis and ultimately survival in this experimental murine model of lethal sepsis. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is used in Hong Kong to provide additional circulation and respiratory support to patients. Exposure to toxins could cause profound shock and respiratory failure. The role of using ECMO to support severe circulatory and respiratory failure in patients with a toxicological cause of admission in Hong Kong is explored in this study. Objective: This study aims to describe the local practice of the use of ECMO in poisoning in Hong Kong. Method: This was a retrospective analysis of patients receiving ECMO for toxicological‐related causes between January 2013 and December 2023. Indications, the poisons of concern, and the mortality of the patients were reviewed. Results: We reported a total of 20 cases during the study period. Fourteen of them received VA‐ECMO, and six of them received VV‐ECMO. The most common poisons in patients receiving VA‐ECMO were calcium channel blockers and beta blockers. The ICU mortality rate for patients receiving VV‐ECMO was 16.6%, whereas it was 42.8% for those receiving VA‐ECMO. Of the 4 patients who received ECPR, the mortality rate was 75%. Most of the patients who survived had excellent cerebral performance category at 3 months. Conclusion: ECMO might be a useful modality for providing temporary respiratory and circulatory support to poisoned patients. [ABSTRACT FROM AUTHOR]

Background: To describe the characteristics of pediatric patients with severe COVID‐19 in China and identify the clinical variables associated with cardiovascular involvement, severe neurological complications, and disease prognosis. Methods: A retrospective surveillance study were conducted from December 1 to 31, 2022, in Guangzhou Women and Children's Medical Center. Clinical and laboratory characteristics were abstracted by medical record review and were further analyzed according to different manifestations. Results: A total of 30 children (median age, 27.5 months; 36.7% female) met the criteria for the diagnosis of severe COVID‐19. The top five presented symptoms were fever, convulsions, cough, polypnea, and fatigue. Compared with shock absent patients, the cardiovascular involved patients had different laboratory features, including elevated aspartate aminotransferase (AST), lactic acid levels, and abnormalities in coagulation parameters. Higher levels of alanine aminotransferase, AST, lactic dehydrogenase, creatinine, lactic acid, and abnormal coagulant function were more common in patients with severe neurological complications and patients who died during hospitalization. Higher lymphocyte counts and serum sodium concentrations were also observed in non‐survivors. Conclusion: Severe COVID‐19 pediatric patients had varied clinical characteristics. Laboratory features associated with cardiovascular involvement, severe neurological complications, and adverse outcomes may facilitate early identification of the severe patients. [ABSTRACT FROM AUTHOR]

Vasopressor therapy represents a key part of intensive care patient management, used to increase and maintain vascular tone and thus adequate tissue perfusion in patients with shock. Norepinephrine is the preferred first-line agent because of its reliable vasoconstrictor effects, with minimal impact on heart rate, and its mild inotropic effects, helping to maintain cardiac output. Whichever vasopressor is used, its effects on blood flow must be considered and excessive vasoconstriction avoided. Other vasoactive agents include vasopressin, which may be considered in vasodilatory states, and angiotensin II, which may be beneficial in patients with high renin levels, although more data are required to confirm this. Dobutamine should be considered, along with continued fluid administration, to help maintain adequate tissue perfusion in patients with reduced oxygen delivery. In this narrative review, we consider the different vasopressor agents, focusing on the importance of tailoring therapy to the individual patient and their hemodynamic response. [ABSTRACT FROM AUTHOR]

This review explores the current landscape and evolving understanding of sepsis, highlighting both challenges and future directions. Sepsis remains a major global health burden, with diverse clinical presentations complicating timely diagnosis and management. Existing definitions, including the Sepsis-3 criteria, emphasize the importance of organ dysfunction, yet early sepsis detection remains limited by available tools. The Sequential Organ Failure Assessment (SOFA) score, though widely used, may not fully capture early stages of infection or account for complex presentations like noncatecholamine-resistant shock. Additionally, the review underscores the pressing need for standardized terminology across sepsis and shock characterization to ensure consistency in diagnosis and treatment strategies. Accessible, resource-adapted solutions are particularly crucial in low- and middle-income countries where sepsis-related mortality rates are higher due to limited resources. Future research should focus on developing and validating integrated, multi-parameter tools that combine clinical, biochemical, and microbiological data to improve sepsis outcomes globally. Advancing sepsis care will require both technological innovation and collaborative, globally consistent guidelines to bridge disparities in healthcare delivery. [ABSTRACT FROM AUTHOR]

The effect of secondary gas injection on the flow through an axisymmetric Mach 2 nozzle is studied experimentally. The experiments were conducted for a nozzle pressure ratio of 5. The secondary injection locations chosen for this study were Ls = 0.5Ld and 0.75Ld, and the secondary gas was injected at secondary pressure ratios (SPR) 0.5, 1.0, and 1.5. It is found that for injection at 0.5 Ld, the flow emanating is not deflected for all SPRs. For injection at 0.75 Ld, the flow is deflected by about 5.50, 5.50 and 100, for SPRs 0.5, 1.0, and 1.5, respectively. These flow deflections are observed only in the plane of injection. The effect of secondary injection was not observed in the plane normal to the secondary injection. [ABSTRACT FROM AUTHOR]

To summarize the evidence of the hemodynamic effects and vasopressor requirements of adult cardiac surgery patients with vasoplegic shock treated with hydroxocobalamin or methylene blue. Systematic review and meta-analysis. Multi-institutional. Adult cardiac surgery patients with vasoplegic shock. Administration of hydroxocobalamin or methylene blue. A total of 263 patients in four retrospective observational studies were included in a pooled analysis. There was no significant difference in the primary outcome, vasopressor requirement at 1 hour (mean difference [MD]: 0.00 mcg/kg/min norepinephrine equivalent [NEE], 95% confidence interval [CI]: –0.09 to 0.08). Hydroxocobalamin was associated with a significant improvement in mean arterial pressure at 1 hour (MD: 5.30 mmHg, 95% CI: 2.98 to 7.62), total vasopressor dose at 1 hour (MD: –0.13 mcg/kg/min NEE, 95% CI: –0.25 to –0.01), total vasopressor at 6 hours (MD: –0.15 mcg/kg/min NEE, 95% CI: –0.21 to –0.08). No differences were observed in systemic vascular resistance or mortality between groups. Three studies were deemed at moderate risk of bias and one at serious risk. Hydroxocobalamin has been shown to have a beneficial effect on hemodynamics and vasopressor requirements in vasoplegic cardiac surgery patients compared with methylene blue, although evidence is limited, and further well-powered randomized controlled trials are required. [ABSTRACT FROM AUTHOR]

Purpose: The compensatory reserve metric (CRM) is a novel tool to predict cardiovascular decompensation during hemorrhage. The CRM is traditionally computed using waveforms obtained from photoplethysmographic volume-clamp (PPGVC), yet invasive arterial pressures may be uniquely available. We aimed to examine the level of agreement of CRM values computed from invasive arterial-derived waveforms and values computed from PPGVC-derived waveforms. Methods: Sixty-nine participants underwent graded lower body negative pressure to simulate hemorrhage. Waveform measurements from a brachial arterial catheter and PPGVC finger-cuff were collected. A PPGVC brachial waveform was reconstructed from the PPGVC finger waveform. Thereafter, CRM values were computed using a deep one-dimensional convolutional neural network for each of the following source waveforms; (1) invasive arterial, (2) PPGVC brachial, and (3) PPGVC finger. Bland-Altman analyses were used to determine the level of agreement between invasive arterial CRM values and PPGVC CRM values, with results presented as the Mean Bias [95% Limits of Agreement]. Results: The mean bias between invasive arterial- and PPGVC brachial CRM values at rest, an applied pressure of -45mmHg, and at tolerance was 6% [-17%, 29%], 1% [-28%, 30%], and 0% [-25%, 25%], respectively. Additionally, the mean bias between invasive arterial- and PPGVC finger CRM values at rest, applied pressure of -45mmHg, and tolerance was 2% [-22%, 26%], 8% [-19%, 35%], and 5% [-15%, 25%], respectively. Conclusion: There is generally good agreement between CRM values obtained from invasive arterial waveforms and values obtained from PPGVC waveforms. Invasive arterial waveforms may serve as an alternative for computation of the CRM. [ABSTRACT FROM AUTHOR]

Sodium-glucose transporter 2 (SGLT2) inhibitors such as empagliflozin are one of the main treatments for type 2 diabetes mellitus (DM2) and heart failure (HF). They have also demonstrated anti-arrhythmic effects in some preclinical and clinical studies. The purpose of this study was to assess the effects of empagliflozin on ventricular arrhythmias in HF patients with an implantable cardioverter-defibrillator (ICD). In a prospective double-blinded, randomized controlled trial of Iran County, Mashhad (72 patients 1:1), we compared the frequency and proportion of ventricular arrhythmias and ICD therapies during the 24 weeks to the prior 24 weeks. Results revealed that empagliflozin significantly reduced the frequency and proportion of ventricular tachycardia (VT)/fibrillation (VF) episodes (P = 0.019 and 0.039, respectively). Moreover, it tended to reduce the frequency and proportion of ICD therapies, including anti-tachycardia pacing (ATP) and shock. Subgroup analysis of patients with or without any antiarrhythmic drugs (digoxin, mexiletine, amiodarone, or sotalol) revealed that only patients who were previously on the antiarrhythmic drugs benefit from empagliflozin antiarrhythmic effects. In conclusion, empagliflozin exhibits anti-arrhythmic effects in HF patients with an ICD. Larger and long-term clinical studies are still needed to investigate and confirm all positive effects of SGLT2 inhibitors in this regard. Trial registration number: IRCT20120520009801N7 (Approval date: June 11, 2022). [ABSTRACT FROM AUTHOR]

Background: The case fatality rate of untreated dengue is 20%; it can be reduced to less than 1% with optimal management. The leading causes of death in dengue patients are shock, bleeding, and acute liver injury. We describe the clinical features of patients who died of dengue and discuss the therapeutic challenges and pitfalls of complicated dengue. Methods: This retrospective study was done in the intensive care unit (MICU) of the National Hospital of Sri Lanka over 30 months between 2021 and 2023. All patients who died of serologically confirmed dengue were incorporated. Results: Of the 1722 ICU admissions, 44 (2.6%) patients were treated for dengue—of them, 11 (25.0%) died. Two patients were excluded as their deaths were not directly linked to dengue. Six were females. The average age was 40.2 years. The leading causes of death included shock (n = 5), acute liver failure (n = 6), intracranial bleeding (n = 2), and pulmonary embolism (n = 1). Patient 1 had concomitant leakage and bleeding, which did not respond to fluids or blood products. He developed fluid overload and acute liver failure (ALF) and died of multiorgan dysfunction. Patients 2–5 were in shock for a prolonged period due to leakage ± bleeding. Patients 2–5 developed ALF and lactic acidosis followed by multiorgan dysfunction. Patient 8 developed acute hepatitis and ALF without preceding shock. The patient was treated with immunosuppressants for myasthenia gravis. Patients 6 and 7 experienced intracranial bleeding. Patient 9 died of pulmonary embolism after prolonged ventilation for dengue encephalitis. Conclusions: Prolonged shock, fluid overload and acute liver failure were common causes of dengue related deaths, in our study. Fluid overload occurred when vigorous crystalloid resuscitation was continued in patients who were poorly responding. A prompt switch to colloids or blood could have prevented overload. Patients who were in shock for a prolonged period become unresponsive to fluid resuscitation. How to manage dengue in patients who take anti-inflammatory drugs, immunomodulators, or antiplatelets is not known. Balancing the bleeding risk of dengue in patients predisposed to bleeding or thrombosis is a challenge. [ABSTRACT FROM AUTHOR]

This review discusses the pivotal role of microcirculation in maintaining tissue oxygenation and waste removal and highlights its significance in various pathological conditions. It delves into the cellular mechanisms underlying hemodynamic coherence, elucidating the roles of the endothelium, glycocalyx, and erythrocytes in sustaining microcirculatory integrity. Furthermore, the review gives comprehensive information about microcirculatory changes observed in cardiac surgery, sepsis, shock, and COVID-19 disease. Through comprehensive exploration, the review underscores the intricate relationship between microcirculation, disease states, and clinical outcomes, emphasizing the importance of understanding and monitoring microvascular dynamics in critical care settings. [ABSTRACT FROM AUTHOR]

The present paper establishes a local well-posed result for piecewise regular solutions with single shock of scalar balance laws with singular integral of convolution type kernels. In a neighborhood of the shock curve, a detailed description of the solution is provided for a general class of initial data. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Left ventricular (LV) unloading is a crucial intervention to decrease the harmful consequences of extracorporeal membrane oxygenation (ECMO) on hemodynamic status in cardiogenic shock (CS) patients. However, a lingering question preoccupies experts: Should we intervene early or wait until clinical deterioration caused by increasing afterload is detected?A systematic review and meta‐analysis synthesizing studies, which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through December 2023. We used R V. 4.3 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42024501643.Eight studies with 2.117 patients were included. Early/prophylactic LV unloading was associated with a lower incidence of all‐cause mortality [RR: 0.87 with 95% CI (0.79, 0.95), p < 0.01]. However, there was no significant difference between the two groups regarding cardiac mortality [RR: 1.01 with 95% CI (0.68, 1.48), p = 0.98], non‐cardiac mortality [RR: 0.86 with 95% CI (0.46, 1.62), p = 0.64], and in‐hospital mortality [RR: 0.95 with 95% CI (0.86, 1.05), p = 0.30]. There was no significant difference between the two groups regarding ECMO weaning, myocardial recovery, ECMO duration, and length of hospitalization.Early/prophylactic LV unloading during ECMO for CS patients was associated with a decreased incidence of all‐cause mortality and sepsis or infection, with no effect on ECMO weaning, myocardial recovery, ECMO duration, and hospital length of stay. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively study the use of the human‐based Trauma‐Associated Severe Hemorrhage (TASH) score to predict transfusion needs and outcome in a population of traumatized dogs. Measurements and Main Results: The TASH score (comprising sex, hemoglobin concentration, systolic blood pressure, abdominal effusion, heart rate, base excess [BE], and presence of pelvic/femoral fractures) was applied to 24 dogs presenting to a private veterinary hospital following trauma: 12 dogs that required transfusion of blood products and 12 age‐ and weight‐matched controls that did not. Dogs that required transfusions demonstrated a significantly higher TASH score compared with dogs that did not (10.2 ± 2.0 vs 5.2 ± 1.1, respectively; P = 0.03). Univariate analyses of individual TASH score components demonstrated significant differences between animals that received a transfusion and those that did not in BE (median: −8.6 [range: −14.4 to 1.4] vs −4.5 [range: −15.4 to −0.4], respectively; P = 0.04) and positive abdominal fluid score (4/12 vs 0/12, respectively; P = 0.03). The Animal Trauma Triage scores (ATTSs) for dogs included in the study were also obtained from the Veterinary Committee on Trauma registry. The mean ATTS was significantly higher in dogs that received blood transfusions than those that did not (5.2 ± 0.78 vs 2.0 ± 0.5, respectively; P = 0.003). Conclusions: The TASH score may be useful to predict transfusion needs in a larger population of traumatized canine patients. [ABSTRACT FROM AUTHOR]

Implantable cardioverter defibrillators (ICDs) are implanted in increasing numbers of patients with the aim of treating ventricular arrhythmias in high-risk patients and reducing their risk of dying. Individuals are also living longer with these devices. As a result, a greater number of patients with an ICD will deteriorate either with worsening cardiac failure, another non-cardiac condition or general frailty and will have a limited prognosis. Frequently, they will be cared for by non-cardiac teams who may be less familiar with ICDs. Therefore, to ensure the person receives high-quality end-of-life care, they should have the opportunity to consider and discuss the option to deactivate the shock function of their ICD. If the ICD shock therapy is not discontinued, there is an increased risk that, as a person reaches the last days of life, the ICD may deliver multiple, painful shocks that are distressing. There is also a risk that the device may delay the person's natural death, which the person would not have chosen if they had been given the opportunity to discuss discontinuation. The British Heart Rhythm Society has developed a practical guideline to support all healthcare professionals who are caring for patients who have an ICD. This includes descriptions of different device types, ethical and legal aspects, timing and nature of ICD discussions and practical advice regarding how the devices may be deactivated. It aims to promote awareness and timely discussion between professionals and patients and to encourage best practice. [ABSTRACT FROM AUTHOR]

Hemorrhage leading to life-threatening shock is a common and critical problem in both civilian and military medicine. Due to complex physiological compensatory mechanisms, traditional vital signs may fail to detect patients' impending hemorrhagic shock in a timely manner when life-saving interventions are still viable. To address this shortcoming of traditional vital signs in detecting hemorrhagic shock, we have attempted to identify metrics that can predict blood loss. We have previously combined feature extraction and machine learning methodologies applied to arterial waveform analysis to develop advanced metrics that have enabled the early and accurate detection of impending shock in a canine model of hemorrhage, including metrics that estimate blood loss such as the Blood Loss Volume Metric, the Percent Estimated Blood Loss metric, and the Hemorrhage Area metric. Importantly, these metrics were able to identify impending shock well before traditional vital signs, such as blood pressure, were altered enough to identify shock. Here, we apply these advanced metrics developed using data from a canine model to data collected from a swine model of controlled hemorrhage as an interim step towards showing their relevance to human medicine. Based on the performance of these advanced metrics, we conclude that the framework for developing these metrics in the previous canine model remains applicable when applied to a swine model and results in accurate performance in these advanced metrics. The success of these advanced metrics in swine, which share physiological similarities to humans, shows promise in developing advanced blood loss metrics for humans, which would result in increased positive casualty outcomes due to hemorrhage in civilian and military medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemosaturation for inoperable liver tumors can improve survival but often causes circulatory problems during filtration, making management challenging. In a study of 66 cases from 2016 to 2024, two approaches were compared: group 1 used one type of vasoactive drug (norepinephrine) and colloids, while group 2 used two types of vasoactive drugs (norepinephrine, vasopressin) and balanced crystalloids instead of colloids. Group 2 showed higher heart rates and lower blood pressure during filtration, with a higher dose of vasoactive drugs. Group 1 had higher lactate levels and used more blood products, while group 2 showed lower platelet counts. Both approaches showed no peri-interventional mortality. High-dose vasoactive drug use including vasopressin and balanced crystalloids is sufficient to stabilize circulatory function during chemosaturation. Background: Hepatic chemosaturation for inoperable liver tumors is a palliative treatment option with a beneficial effect on survival. However, the procedure regularly leads to circulatory failure during the filtration phase, and hemodynamic management is challenging. Our study aimed to compare two different strategies for hemodynamic management during chemosaturation to develop hypotheses for improving patient care and reducing peri-interventional morbidity. Methods: We conducted a single-center retrospective cohort study including 66 procedures of chemosaturation between May 2016 and March 2024. Procedures were divided into two groups: group 1 was managed with norepinephrine as the only vasopressor and liberal use of hydroxyethyl starch (HES). Group 2 was managed with norepinephrine and vasopressin and the preferred use of balanced crystalloids. We compared these two groups with respect to hemodynamic parameters, laboratory values, and post-interventional complications. Results: The heart rate was highest and the mean arterial pressure (MAP) was lowest during the filtration phase in both groups (p = 0.868, p = 0.270). The vasoactive inotropic score (VIS) was significantly higher in group 2 during the filtration phase (31.5 vs. 89, p < 0.001). Group 1 received significantly more HES overall (1000 mL vs. 0 mL, p < 0.001). Lactate levels at admission to the ICU were higher in group 1 (22.9 vs. 14.45 mg/dL, p = 0.041). Platelet counts were lower in group 2 from directly after chemosaturation through day 2 (p = 0.022, p = 0.001, p = 0.032). The INR differed significantly directly after chemosaturation (1.13 vs. 1.26, p = 0.015). Overall, group 1 received significantly more blood products peri-interventionally. There were two bleedings and one ischemic stroke in the overall cohort. There was no peri-interventional mortality. Conclusions: Advanced hemodynamic management ensures low peri-interventional mortality and morbidity. High-dose vasopressors, including vasopressin and the preferred use of balanced crystalloids, are sufficient to stabilize circulatory function during chemosaturation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objectives of our systematic review and meta-analyses were to determine the diagnostic accuracy of central venous oxygen saturation (Scvo2) in estimating mixed venous oxygen saturation (Svo2) and cardiac index in critically ill patients. DATA SOURCES: A systematic search using MEDLINE, Cochrane Central Register of Controlled Trials, and Embase was completed on May 6, 2024. STUDY SELECTION: Studies of patients in the ICU for whom Scvo2 and at least one reference standard test was performed (thermodilution and/or Svo2) were included. DATA EXTRACTION: Individual patient data were used to calculate the pooled intraclass correlation coefficient (ICC) for Svo2 and Spearman correlation for cardiac index. The Quality Assessment of Diagnostic Accuracy Studies-2 and Grading Recommendations Assessment, Development, and Evaluation tools were used for the risk of bias and certainty of evidence assessments. DATA SYNTHESIS: Of 3427 studies, a total of 18 studies with 1971 patients were identified. We meta-analyzed 16 studies (1335 patients) that used Svo2 as a reference and three studies (166 patients) that used thermodilution as reference. The ICC for reference Svo2 was 0.83 (95% CI, 0.75-0.89) with a mean difference of 2.98% toward Scvo2. The Spearman rank correlation for reference cardiac index is 0.47 (95% CI, 0.46-0.48; p < 0.0001). CONCLUSIONS: There is moderate reliability for Scvo2 in predicting Svo2 in critical care patients with variability based on sampling site and presence of sepsis. There is limited evidence on the independent use of Scvo2 in predicting cardiac index. [ABSTRACT FROM AUTHOR]

The article "Unlocking the Potential: Can Point-of-Care Ultrasound-Guided Resuscitation Impact the Clinical Care for Adults With Shock?" published in Critical Care Medicine discusses the use of point-of-care ultrasound (POCUS) in managing critically ill patients with shock. The study found that POCUS-guided resuscitation led to a reduction in 28-day mortality rates, but other outcomes such as hospital length of stay showed mixed results. The article emphasizes the need for enhanced training methods, practical strategies for incorporating POCUS into daily practice, and the appropriate utilization of POCUS throughout a patient's care to fully realize its potential in shock management. [Extracted from the article]

OBJECTIVE: To determine the impact of point-of-care ultrasound (POCUS)- guided resuscitation on clinical outcomes in adult patients with shock. DATA SOURCE: We searched MEDLINE, Embase, and unpublished sources from inception to December 2023. STUDY SELECTION: We included randomized controlled trials (RCTs) that examined the use of POCUS to guide resuscitation in patients with shock. DATA EXTRACTION: We collected data regarding study and patient characteristics, POCUS protocol, control group interventions, and outcomes. DATA SYNTHESIS: We identified 18 eligible RCTs. POCUS slightly influences physicians' plans for IV fluid (IVF) and vasoactive medication prescription (moderate certainty), but results in little to no changes in the administration of IVF (low to high certainty) or inotropes (high certainty). POCUS may result in no change in the number of CT scans performed (low certainty) but probably reduces the number of diagnostic echocardiograms performed (moderate certainty). POCUSguided resuscitation probably reduces 28-day mortality (relative risk [RR] 0.88; 95% CI, 0.78-0.99), the duration of vasoactive medication (mean difference -0.73 d; 95% CI, -1.16 to -0.30), and the need for renal replacement therapy (RRT) (RR 0.80; 95% CI, 0.63-1.02) (low to moderate certainty evidence), and lactate clearance (high certainty evidence). POCUS-guided resuscitation may results in little to no difference in ICU or hospital admissions, ICU and hospital length of stay, and the need for mechanical ventilation (MV) (low to moderate certainty evidence). There is an uncertain effect on the risk of acute kidney injury and the duration of MV or RRT (very low certainty evidence). CONCLUSIONS: POCUS-guided resuscitation in shock may yield important patient and health system benefits. Due to lack of sufficient evidence, we were unable to explore how the thresholds of operator competency, frequency, and timing of POCUS scans impact patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to describe the implementation and outcomes of a protocol outlining angiotensin-II utilization for vasoplegia following cardiac surgery. Methods: This was a retrospective chart review at a single-center university hospital. Included patients received angiotensin-II for vasoplegia refractory to standard interventions, including norepinephrine 20 mcg/min and vasopressin 0.04 units/min, following cardiac surgery between April 2021 and April 2022. Results: 30 patients received angiotensin-II for refractory vasoplegia. Adjunctive agents at angiotensin-II initiation included corticosteroids (26 patients; 87%), epinephrine (26 patients; 87%), dobutamine (17 patients; 57%), dopamine (9 patients; 30%), milrinone (2 patients; 7%), and hydroxocobalamin (4 patients; 13%). At 3 hours, the median mean arterial pressure increased from baseline (70 vs 61.5 mmHg, p =.0006). Median norepinephrine doses at angiotensin-II initiation, 1 hour, 3 hours, and angiotensin-II discontinuation were 0.22, 0.16 (p =.0023), 0.10 (p <.0001), and 0.07 (p <.0001) mcg/kg/min. Median dobutamine doses decreased throughout angiotensin-II infusion from eight to six mcg/kg/min (p =.0313). Other vasoactive medication doses were unchanged. Three patients (10%) subsequently received hydroxocobalamin. Thirteen (43.3%) and five (16.7%) patients experienced mortality by day 28 and venous or arterial thrombosis events, respectively. Conclusions: The administration of angiotensin-II to vasoplegic patients following cardiac surgery was associated with increased mean arterial pressure, reduced norepinephrine dosages, and reduced dobutamine dosages. [ABSTRACT FROM AUTHOR]

Objectives: Post‐cardiotomy extracorporeal life support (ECLS) cannulation might occur in a general post‐operative ward due to emergent conditions. Its characteristics have been poorly reported and investigated This study investigates the characteristics and outcomes of adult patients receiving ECLS cannulation in a general post‐operative cardiac ward. Methods: The Post‐cardiotomy Extracorporeal Life Support (PELS) is a retrospective (2000–2020), multicenter (34 centers), observational study including adult patients who required ECLS for post‐cardiotomy shock. This PELS sub‐analysis analyzed patients´ characteristics, in‐hospital outcomes, and long‐term survival in patients cannulated for veno‐arterial ECLS in the general ward, and further compared in‐hospital survivors and non‐survivors. Results: The PELS study included 2058 patients of whom 39 (1.9%) were cannulated in the general ward. Most patients underwent isolated coronary bypass grafting (CABG, n = 15, 38.5%) or isolated non‐CABG operations (n = 20, 51.3%). The main indications to initiate ECLS included cardiac arrest (n = 17, 44.7%) and cardiogenic shock (n = 14, 35.9%). ECLS cannulation occurred after a median time of 4 (2–7) days post‐operatively. Most patients' courses were complicated by acute kidney injury (n = 23, 59%), arrhythmias (n = 19, 48.7%), and postoperative bleeding (n = 20, 51.3%). In‐hospital mortality was 84.6% (n = 33) with persistent heart failure (n = 11, 28.2%) as the most common cause of death. No peculiar differences were observed between in‐hospital survivors and nonsurvivors. Conclusions: This study demonstrates that ECLS cannulation due to post‐cardiotomy emergent adverse events in the general ward is rare, mainly occurring in preoperative low‐risk patients and after a postoperative cardiac arrest. High complication rates and low in‐hospital survival require further investigations to identify patients at risk for such a complication, optimize resources, enhance intervention, and improve outcomes. [ABSTRACT FROM AUTHOR]

Thiamine is an essential micronutrient for energy metabolism. Thiamine deficiency is frequently observed in critically ill patients. However, the effect of thiamine administration is unclear in critically ill patients. We conducted a systematic review and meta-analysis. To identify randomized controlled trials on the effect of thiamine administration in critically ill patients, a literature search was conducted in MEDLINE, CENTRAL, and ICHUSHI databases from inception to April 2023. Pooled effect estimates were calculated about mortality as the primary outcome and shock duration, lactate level, Sequential Organ Failure Assessment (SOFA) score, delirium, length of mechanical ventilation, length of intensive care unit (ICU) stay, infection rate, all adverse events, and Short-Form Health Survey (SF-36) as the secondary outcomes. The certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Overall, 35 studies (3494 patients) were included. Evidence suggested that thiamine administration resulted in little to no difference in mortality (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.75 to 1.06; Low CoE); however, thiamine administration may reduce shock duration (mean difference [MD], −11.43 h; 95% CI, −20.16 to −2.69 h; Low CoE), lactate level (MD, −0.34 mmol/L; 95% CI, −0.63 to −0.05 mmol/L; Low CoE), and SOFA score (MD, −1.29; 95% CI, −1.91 to −0.66; Low CoE). Conversely, thiamine administration resulted in a slight increase in the length of ICU stay (MD, 0.40 days; 95% CI, 0.01–0.79 days; High CoE). Although thiamine administration may reduce shock state, it may not reduce mortality, and slightly increases the length of ICU stay. [ABSTRACT FROM AUTHOR]

During recovery from septic shock, circulating mitochondrial N -formyl peptides predispose to secondary infection by occupying formyl peptide receptor 1 on the neutrophil (polymorphonuclear leukocyte) membrane, suppressing cytosolic calcium ([Ca2+]i)-dependent responses to secondarily encountered bacteria. However, no study has yet investigated therapeutic clearance of circulating mitochondrial N -formyl peptides in clinical settings. Thus, we studied how to remove mitochondrial N -formyl peptides from septic-shock plasma and whether such removal could preserve cell-surface formyl peptide receptor 1 and restore sepsis-induced polymorphonuclear leukocyte dysfunction by normalizing [Ca2+]i flux. In in vitro model systems, mitochondrial N -formyl peptide removal rescued polymorphonuclear leukocyte formyl peptide receptor 1-mediated [Ca2+]i flux and chemotaxis that had been suppressed by prior mitochondrial N -formyl peptide exposure. However, polymorphonuclear leukocyte functional recovery occurred in a stepwise fashion over 30 to 90 min. Intracellular Ca2+-calmodulin appears to contribute to this delay. In ex vivo model, systems using blood samples obtained from patients with septic shock, antimitochondrial N -formyl peptide antibodies alone failed to eliminate mitochondrial N -formyl peptides from septic-shock plasma or inhibit mitochondrial N -formyl peptide activity. We therefore created a beads-based antimitochondrial N -formyl peptide antibody cocktail by combining protein A/sepharose with antibodies specific for the most potent human mitochondrial N -formyl peptide chemoattractants. The beads-based antimitochondrial N -formyl peptide antibody cocktail treatment successfully removed those active mitochondrial N -formyl peptides from septic-shock plasma. Furthermore, the beads-based antimitochondrial N -formyl peptide antibody cocktail treatment significantly restored chemotactic and bactericidal dysfunction of polymorphonuclear leukocytes obtained from patients with septic shock who developed secondary infections. By clearing circulating mitochondrial N -formyl peptides, the immobilized antimitochondrial N -formyl peptide antibody therapy prevented mitochondrial N -formyl peptide interactions with surface formyl peptide receptor 1, thereby restoring [Ca2+]i-dependent polymorphonuclear leukocyte antimicrobial function in clinical septic-shock environments. This approach may help prevent the development of secondary, nosocomial infections in patients recovering from septic shock. [ABSTRACT FROM AUTHOR]

Importance: Decision-making in trauma patients remains challenging and often results in deviation from guidelines. Machine-Learning (ML) enhanced decision-support could improve hemorrhage resuscitation. Aim: To develop a ML enhanced decision support tool to predict Need for Hemorrhage Resuscitation (NHR) (part I) and test the collection of the predictor variables in real time in a smartphone app (part II). Design, setting, and participants: Development of a ML model from a registry to predict NHR relying exclusively on prehospital predictors. Several models and imputation techniques were tested. Assess the feasibility to collect the predictors of the model in a customized smartphone app during prealert and generate a prediction in four level-1 trauma centers to compare the predictions to the gestalt of the trauma leader. Main outcomes and measures: Part 1: Model output was NHR defined by 1) at least one RBC transfusion in resuscitation, 2) transfusion ≥ 4 RBC within 6 h, 3) any hemorrhage control procedure within 6 h or 4) death from hemorrhage within 24 h. The performance metric was the F4-score and compared to reference scores (RED FLAG, ABC). In part 2, the model and clinician prediction were compared with Likelihood Ratios (LR). Results: From 36,325 eligible patients in the registry (Nov 2010—May 2022), 28,614 were included in the model development (Part 1). Median age was 36 [25–52], median ISS 13 [5–22], 3249/28614 (11%) corresponded to the definition of NHR. A XGBoost model with nine prehospital variables generated the best predictive performance for NHR according to the F4-score with a score of 0.76 [0.73–0.78]. Over a 3-month period (Aug—Oct 2022), 139 of 391 eligible patients were included in part II (38.5%), 22/139 with NHR. Clinician satisfaction was high, no workflow disruption observed and LRs comparable between the model and the clinicians. Conclusions and relevance: The ShockMatrix pilot study developed a simple ML-enhanced NHR prediction tool demonstrating a comparable performance to clinical reference scores and clinicians. Collecting the predictor variables in real-time on prealert was feasible and caused no workflow disruption. [ABSTRACT FROM AUTHOR]

Shock is a life-threatening condition. This study evaluated if sublingual microcirculatory perfusion on admission is associated with 30-day mortality in older intensive care unit (ICU) shock patients. This trial prospectively recruited ICU patients (≥ 80 years old) with arterial lactate above 2 mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of shock cause. All patients received sequential sublingual measurements on ICU admission (± 4 h) and 24 (± 4) hours later. The primary endpoint was 30-day mortality. From September 4th, 2022, to May 30th, 2023, 271 patients were screened, and 44 included. Patients were categorized based on the median percentage of perfused small vessels (sPPV) into those with impaired and sustained microcirculation. 71% of videos were of good or acceptable quality without safety issues. Patients with impaired microcirculation had significantly shorter ICU and hospital stays (p = 0.015 and p = 0.019) and higher 30-day mortality (90.0% vs. 62.5%, p = 0.036). Cox regression confirmed the independent association of impaired microcirculation with 30-day mortality (adjusted hazard ratio 3.245 (95% CI 1.178 to 8.943, p = 0.023). Measuring sublingual microcirculation in critically ill older patients with shock on ICU admission is safe, feasible, and provides independent prognostic information about outcomes. Trial registration NCT04169204. [ABSTRACT FROM AUTHOR]

Background: Rasburicase, a recombinant urate oxidase enzyme, has potent efficacy in controlling uric acid and is widely used to prevent tumor lysis syndrome in high-risk patients owing to its low toxicity profile. However, it has been associated with a risk of anaphylaxis, especially on re-exposure, owing to its immunogenic potential. Case presentation: A 71-year-old Japanese female diagnosed with diffuse large B cell lymphoma with a large tumor burden experienced anaphylactic shock leading to death upon initial administration of rasburicase. The pre-and postmortem examination revealed that the cause of death was a cascade of events starting with anaphylaxis-induced distributive shock leading to obstructive shock due to the collapse of the heart, which was compressed by the post-mediastinal tumor. This was further compounded by massive bleeding from the tumor and tension hemothorax, resulting in circulatory collapse. Conclusions: Although extremely rare, rasburicase can cause fatal anaphylaxis, even on first exposure. [ABSTRACT FROM AUTHOR]

Rationale: Allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) recipients are still believed to be poor candidates for ICU management. Methods: We investigated outcomes and determinants of mortality in a large multicenter retrospective cohort of Allo-HSCT patients admitted between January 1, 2015, and December 31, 2020, to 14 French ICUs. The primary endpoint was 90-day mortality. Measurements and Main Results: In total, 1,164 patients were admitted throughout the study period. At the time of ICU admission, 765 (66%) patients presented with multiple organ dysfunction, including acute respiratory failure in 40% (n = 461). The median sepsis-related organ failure assessment score was 6 (interquartile range, 4–8). Invasive mechanical ventilation, renal replacement therapy, and vasopressors were required in 438 (38%), 221 (19%), and 468 (41%) patients, respectively. ICU mortality was 26% (302 deaths). Ninety-day, 1-year, and 3-year mortality rates were 48%, 63%, and 70%, respectively. By multivariable analysis, age > 56 years (odds ratio [OR], 2.0 [95% confidence interval (CI), 1.53–2.60]; P < 0.001), time from Allo-HSCT to ICU admission between 30 and 90 days (OR, 1.68 [95% CI, 1.17–2.40]; P = 0.005), corticosteroid-refractory acute graft-versus-host disease (OR, 1.63 [95% CI, 1.38–1.93]; P < 0.001), need for vasopressors (OR, 1.9 [95% CI, 1.42–2.55]; P < 0.001), and mechanical ventilation (OR, 3.1 [95% CI, 2.29–4.18]; P < 0.001) were independently associated with 90-day mortality. In patients requiring mechanical ventilation, mortality rates ranged from 39% (no other risk factors for mortality) to 100% (four associated risk factors for mortality). Conclusions: Most critically ill Allo-HSCT recipients survive their ICU stays, including those requiring mechanical ventilation, with an overall 90-day survival rate reaching 51.8%. A careful assessment of goals of care is required in patients with two or more risk factors for mortality. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a sudden, life-threatening hypersensitivity reaction with multiorgan manifestations that requires urgent intervention. Globally, there is an observed increase in hospitalizations due to anaphylactic shock, particularly in children. Despite this increase, mortality rates remain stable or even show a tendency to decrease, estimated within the range of 0.5 to 1.0 deaths per million populations. Hypersensitivity reactions occur in response to an allergen, with the most common causes being nutritional allergens, insect bites, and medications. Anaphylactic shock, as the most severe form of anaphylaxis, is characterized by a significant decrease in blood pressure that can lead to circulatory failure. The key to successful treatment is timely recognition of symptoms, cessation of contact with the allergen and rapid application of appropriate medical therapy. Adrenaline (epinephrine) is considered the first and most important drug in the treatment of anaphylactic shock; therefore, its administration must not be delayed. The aim of these clinical guidelines is to present a recommended algorithm for the diagnosis and treatment of anaphylaxis and anaphylactic shock. [ABSTRACT FROM AUTHOR]

Introduction: Use of albumin is suggested for some patients with shock, but preferences for its use may vary among intensive care unit (ICU) physicians. Methods: We conducted an international online survey of ICU physicians with 20 questions about their use of albumin and their opinion towards a randomised trial among adults with shock comparing the use versus no use of albumin. Results: A total of 1248 respondents participated, with a mean response rate of 37%, ranging from 18% to 75% across 21 countries. Respondents mainly worked in mixed ICUs and 92% were specialists in intensive care medicine. The reported use of albumin in general shock varied as 18% reported 'almost never', 22% 'rarely', 34% 'occasionally', 22% 'frequently' and 4% 'almost always' using albumin. In septic shock, 19% reported 'almost never', 22% 'rarely', 29% 'occasionally', 22% 'frequently' and 7% 'almost always' using albumin. Physicians' preferences were more consistent for haemorrhagic‐ and cardiogenic shock, with more than 45% reporting 'almost never' using albumin. While the reported use of albumin for other purposes than resuscitation was infrequent (40%–85% reported 'almost never' for five other indications), the most frequent other indications were low serum albumin levels and improvement of the efficacy of diuretics. Most respondents (93%) would randomise adult ICU patients with shock to a trial of albumin versus no albumin. Conclusions: In this international survey, the reported preferences for the use of albumin in adult ICU patients with shock varied considerably among surveyed ICU physicians. The support for a future randomised trial was high. [ABSTRACT FROM AUTHOR]

BACKGROUND: A multitude of required and non-necessary changes are linked to infections, and in extreme situations, these changes necessitate prompt attention as infections can be life-threatening and cause serious organ malfunction, which can lead to organ failure and death. Sepsis is a very common and complicated condition and is faced by both the developing and developed world. The global epidemiological burden of sepsis is difficult to ascertain. It is estimated to affect more than 30 million people worldwide every year, potentially leading to 6 million deaths. MATERIALS AND METHODS: A hospital based prospective study was conducted patients admitting in MICU and RICU at Basaveshwara Medical College Hospital, Chitradurga during the study period of 18 months from August 2022 to February 2024. Clearance from institution ethics committee was taken before the study was started. An informed consent was taken before including the study subjects in to the study. RESULTS: There was no statistically significant difference in cases with neutrophil lymphocyte ratio of less and more than 3. There was a statistically significant difference in the neutrophil count in cases with neutrophil lymphocyte ratio of less than 3 and more than 3. There was no statistically significant difference between the cases with neutrophil lymphocyte ratio of less and more than 3 with respect to lymphocyte counts at admission. CONCLUSION: This study was undertaken in order to study neutrophil lymphocyte ratio as a prognostic marker in cases of severe sepsis. This study had shown that, NLR was shown to be an important and readily available marker prognosis of sepsis. But this study is not without limitations. This used a convenience sample method where study results cannot be generalized. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utility of Pulse index Contour Continuous Cardiac Output (PiCCO) monitoring in critically ill patients. Study Design: Cross-sectional study. Setting: Intensive Care Unti of Sindh Institute of Urology and Transplant, Karachi, Pakistan. Period: October 2022 to March 2023. Methods: Patients presenting with various types of shock, requiring high-dose vasopressors or inotropes, and not responding to initial fluid therapy were analyzed. Demographic details, SOFA score, APACHE score, and invasive hemodynamic parameters using the PiCCO system were documented. Results: Out of 142 ICU admissions, 38 patients were included in the study. Most patients were males (73%) with a median age of 39 years. Significant changes were observed in the cardiac index, cardiac performance index, global ejection fraction, and systemic vascular resistance index (SVRI), all with p-values less than 0.05. The interventions included the initiation of inotropes in 22 patients (57.8%), diuretics in 4 patients (10.5%), and intravenous fluids in 19 patients (50%). Additionally, vasopressor doses were adjusted in 18 patients (47.3%). Initially, patients were presumed to have pure septic shock based on CO2 gap, mixed venous saturation, and echocardiographic assessment. However, after applying PiCCO monitoring, the diagnosis was revised to mixed shock in 21 patients (55.2%). Conclusion: PiCCO monitoring appears to be a valuable tool in the ICU for managing patients with complex hemodynamic profiles, facilitating targeted interventions that lead to significant improvements in hemodynamic stability. [ABSTRACT FROM AUTHOR]

Purpose: Echocardiography is recommended as a first-line tool in the assessment of patients with shock. The current provision of echocardiography in critical care is poorly defined. The aims of this work were to evaluate the utilisation of echocardiography in patients presenting to critical care with shock, its impact on decision making, and adherence to governance guidelines. Methods: We conducted a prospective, multi-centre, observational study in 178 critical care units across the United Kingdom (UK) and Crown Dependencies, led by the UK's Trainee Research in Intensive Care Network. Consecutive adult patients (≥ 18 years) admitted with shock were followed up for 72 h to ascertain whether they received an echocardiogram, the nature of any scan performed, and its effect on critical treatment decision making. Results: 1015 patients with shock were included. An echocardiogram was performed on 545 (54%) patients within 72 h and 436 (43%) within 24 h of admission. Most scans were performed by the critical care team (n = 314, 58%). Echocardiography was reported to either reduce diagnostic uncertainty or change management in 291 (54%) cases. Patients with obstructive or cardiogenic shock had their management altered numerically more often by echocardiography (n = 15 [75%] and n = 100 [58%] respectively). Twenty-five percent of echocardiograms performed adhered to current national governance and image storage guidance. Conclusion: Use of echocardiography in the assessment of patients with shock remains heterogenous. When echocardiography is used, it improves diagnostic certainty or changes management in most patients. Future research should explore barriers to increasing use of echocardiography in assessing patients presenting with shock. [ABSTRACT FROM AUTHOR]

Purpose: The Joint Commission standards for titrated infusions require specification of maximum rates of infusion. This practice has led to the development of protocolized maximum doses that can be overridden by provider order ("soft maximums") and to dose caps that cannot be superseded ("hard maximums"). The purpose of this study was to determine the prevalence of and attitudes towards dose capping of norepinephrine. Methods: A 20-item cross-sectional survey assessing norepinephrine dose capping practices, perceptions of norepinephrine protocols, and respondent and practice site demographics was distributed electronically to the mailing list of an international medical podcast. Responses were stratified according to use of weight-based dosing (WBD) or non-WBD of norepinephrine. The primary objective was to characterize norepinephrine dosing practices including protocolized maximum doses and/or dose capping. Categorical and continuous variables were compared using the Chi-square test and Mann-Whitney U test, respectively, with P <.05 indicating statistical significance. Results: The survey was completed by 586 physicians, nurses, pharmacists, and advanced practice providers. WBD was used by 51% and non-WBD by 47%. A standardized titration protocol was reported by 65% and dose capping was reported by 19%. The protocolized maximum dose ranged from 20-400 mcg/min for respondents using non-WBD (median [interquartile range] 30 [30-50]) and ranged from.2-10 mcg/kg/min for respondents using WBD (1 [.5-3]). The dose cap was 50 (40-123) mcg/min with non-WBD and 2 (1-3) mcg/kg/min with WBD. Conclusions: An international, multi-professional survey of critical care and emergency medicine clinicians revealed wide variability in norepinephrine dosing practices including maximum doses allowed. [ABSTRACT FROM AUTHOR]

Shock is a life-threatening clinical condition that arises when there is inadequate oxygen metabolism at a cellular level. It can occur in a wide range of clinical conditions and without prompt identification and management it has a high morbidity and mortality. Treatment focuses on both correcting the cause and managing the abnormal physiology associated with shock. Clinicians use a number of tools including clinical examination, biochemical markers and haemodynamic monitoring to both identify and treat shock. In this article we will review the normal physiology of oxygen delivery, the aetiology and pathophysiology of shock and how haemodynamic monitoring is used to manage patients presenting with shock. [ABSTRACT FROM AUTHOR]

• In those with cardiac amyloidosis and heart failure-related cardiogenic shock, there was significant augmentation of cardiac index after intra-aortic balloon pump (IABP) and significant decreases in left ventricular and right ventricular filling pressures. • Predictors of lack of response to IABP by cardiac index were a smaller baseline left ventricular end-diastolic diameter size per centimeter and higher pre-IABP systemic vascular resistance. • Most patients with Society for Cardiovascular Angiography and Interventions stage C heart failure-related cardiogenic shock were stabilized successfully and bridged to advanced therapies with IABP alone. In those with heart failure-related cardiogenic shock (HF-CS), an intra-aortic balloon pump (IABP) may improve hemodynamics and be useful as a bridge to advanced therapies. We explore whether those with cardiac amyloidosis and HF-CS might experience hemodynamic improvement and describe the hemodynamic response after IABP. We retrospectively identified consecutive patients with a diagnosis of cardiac amyloid, either light chain or transthyretin, who were admitted to our intensive care unit with HF-CS. Patients were excluded if an IABP was placed during heart transplant or for shock related to acute myocardial infarction. Invasive hemodynamics before and after IABP placement were assessed. We identified 23 patients with cardiac amyloid who had an IABP placed for HF-CS. The 1-year survival rate was 74% and most (65%) were bridged to heart transplant, although 1 patient was bridged to destination left ventricular assist device. After IABP, the mean arterial pressure, cardiac index, and cardiac power index were significantly increased, whereas mean right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure were all significantly decreased. A smaller left ventricular end-diastolic diameter (per cm) was associated with a higher likelihood of a cardiac index of <2.2 L/min/m2 after IABP (odds ratio 0.16, 95% confidence interval 0.01–0.93, P =.04). IABP significantly improved cardiac index while decreasing right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure in cardiac amyloidosis patients with HF-CS. [Display omitted] [ABSTRACT FROM AUTHOR]

The 1 Hz whistler wave precursors attached to shock‐like structures are often observed in the foreshock. Using observations from the Magnetospheric Multiscale mission, we investigate the interactions between 1 Hz waves and ions. Incoming solar wind ions do not cyclotron‐resonate with the wave, since typically the wave is right‐handed in their frame. We demonstrate that solar wind ions commonly exhibit 180° gyro‐phase bunching from the wave magnetic field, understanding it with a reconciled linear theory and non‐linear trapping theory for non‐cyclotron‐resonant modulations. Along the longitudinal direction, solar wind ions experience Landau resonance, exhibiting either modulations at small wave potentials or trapping in phase‐space holes at large potentials. The results also improve our understanding of foreshock structure evolution and 1 Hz wave excitation. Shock‐like structures start with having incoming solar wind and remotely reflected ions from further downstream. The ion‐scale 1 Hz waves can already appear during this stage. The excitation may be due to shock‐like dispersive radiation or kinetic instabilities resonant with these remotely reflected ions. Ions reflected by local shock‐like structures occur later, so they are not always necessary for generating 1 Hz waves. The wave leads to ion reflection further upstream, which may cause reformation of shock‐like structures. In one event, locally reflected ions exhibit non‐cyclotron‐resonant modulation in the early stage, and later approach the anomalous cyclotron resonant condition with gyro‐phases ∼270°. The latter is possibly due to nonlinear trapping in regions with an upstream‐pointing magnetic field gradient, linked to reformation. Some additional special features, such as frequency dispersions, are observed, encouraging further investigations. Key Points: Solar wind ions do not gyro‐resonate with 1 Hz whistlers, while they commonly exhibit gyro‐phase bunching and Landau resonance with the waveSLAMS reflected ions show hints of gyro‐resonance with 1 Hz whistlers and losing energy to the fields, with aid of background B gradientWhistler‐ion interactions can cause ion reflections upstream of the main ramp, which in turn modifies shock‐like structures [ABSTRACT FROM AUTHOR]

Objective: The capillary refill test (CR test) is often used in emergency care, and the capillary refill time (CR time) is used to assess a patient's circulatory condition. The objective of this study was to investigate if repeated CR tests affect CR time. Methods: Thirteen healthy volunteers had repeated CR tests performed on the sternum, forehead, and fingers. The tests were filmed using polarized reflectance spectroscopy and dedicated software for objective quantification of the CR time. Results: There were no statistical differences between the first CR test in a series and the following. However, there were statistically significant differences in CR time between the different anatomical sites. Conclusion: Repeated CR tests, separated by a minimum of 2 min, do not affect CR time in healthy volunteers. The site where the test is performed is of importance for CR time. [ABSTRACT FROM AUTHOR]

Abstract Background Sepsis is a condition with high mortality and morbidity, characterized by deregulation of the immune response against the pathogen. Current treatment strategies rely mainly on antibiotics and supportive care. However, there is growing interest in exploring cell-based therapies as complementary approaches. Human liver stem cells (HLSCs) are pluripotent cells of mesenchymal origin, showing some advantages compared to mesenchymal stem cells in terms of immunomodulatory properties. HSLC-derived extracellular vesicles (EVs) exhibited a superior efficacy profile compared to cells due to their potential to get through biological barriers and possibly to avoid tumorigenicity and showed to be effective in vivo and ex vivo models of liver and kidney disease. The potential of HLSCs and their EVs in recovering damage to distal organs due to sepsis other than the kidney remains unknown. This study aimed to investigate the therapeutic potential of the intravenous administration of HSLCs or HSLCs-derived EVs in a murine model of sepsis. Results Sepsis was induced by caecal ligation and puncture (CLP) on C57/BL6 mice. After CLP, mice were assigned to receive either normal saline, HLSCs or their EVs and compared to a sham group which underwent only laparotomy. Survival, persistence of bacteraemia, lung function evaluation, histology and bone marrow analysis were performed. Administration of HLSCs or HLSC-EVs resulted in improved bacterial clearance and lung function in terms of lung elastance and oedema. Naïve murine hematopoietic progenitors in bone marrow were enhanced after treatment as well. Administration of HLSCs and HLSC-EVs after CLP to significantly improved survival. Conclusions Treatment with HLSCs or HLSC-derived EVs was effective in improving acute lung injury, dysmyelopoiesis and ultimately survival in this experimental murine model of lethal sepsis.

Abstract Background Intravenous (IV) vasopressors are the mainstay of physiological support for hemodynamically unstable patients. However, the role of oral vasopressors remains unclear. The objective of our study was to evaluate the feasibility of evaluating midodrine for critically ill patients with IV vasopressor-dependent shock. Methods We conducted a single-center, concealed-allocation, parallel-group, blinded feasibility randomized controlled trial (RCT) evaluating the effect of oral midodrine versus placebo on IV vasopressor-dependent shock in the intensive care unit (ICU). The study was performed in a medical-surgical ICU at the University of Alberta Hospital from April 2021 to July 2022. We included patients aged 18 years or older admitted to the ICU with ongoing vasopressor support with decreasing vasopressor dose(s). Patients were randomly assigned 1:1 to midodrine or a placebo for the duration of their IV vasopressor therapy. The primary outcome was study feasibility and secondary outcomes included patient-centered outcomes. Feasibility was assessed through rate of recruitment, adherence to study protocol, and patient safety. Results Twenty patients were enrolled in the study and underwent randomization (n = 11 midodrine, n = 9 control). Recruitment was recorded at 1.2 participants per month, protocol adherence was 90%, and allocation remained concealed. No adverse events were reported in either group. Sepsis was the most common cause of shock in both groups. The midodrine group had a shorter length of ICU stay of 9.6 (SD 8.7) vs 10.4 (SD 14.5) days. Hospital mortality was lower for the midodrine group (n = 2, 18.2% vs n = 4, 37.5%). Vasopressor re-initiation after 24 h was more frequent in the midodrine group (n = 4, 36.4% vs n = 2, 25%). There were no readmissions to the ICU following discharge in either group. Conclusions The evaluation of midodrine for patients in the ICU is feasible and safe. This trial will inform future large-scale RCTs regarding the utility of midodrine in critically ill patients with IV vasopressor-dependent shock. Trial registration This pilot RCT was registered at clinicaltrials.gov (NCT04489589). Registered July 27, 2020. https://clinicaltrials.gov/study/NCT04489589

Abstract Background The case fatality rate of untreated dengue is 20%; it can be reduced to less than 1% with optimal management. The leading causes of death in dengue patients are shock, bleeding, and acute liver injury. We describe the clinical features of patients who died of dengue and discuss the therapeutic challenges and pitfalls of complicated dengue. Methods This retrospective study was done in the intensive care unit (MICU) of the National Hospital of Sri Lanka over 30 months between 2021 and 2023. All patients who died of serologically confirmed dengue were incorporated. Results Of the 1722 ICU admissions, 44 (2.6%) patients were treated for dengue—of them, 11 (25.0%) died. Two patients were excluded as their deaths were not directly linked to dengue. Six were females. The average age was 40.2 years. The leading causes of death included shock (n = 5), acute liver failure (n = 6), intracranial bleeding (n = 2), and pulmonary embolism (n = 1). Patient 1 had concomitant leakage and bleeding, which did not respond to fluids or blood products. He developed fluid overload and acute liver failure (ALF) and died of multiorgan dysfunction. Patients 2–5 were in shock for a prolonged period due to leakage ± bleeding. Patients 2–5 developed ALF and lactic acidosis followed by multiorgan dysfunction. Patient 8 developed acute hepatitis and ALF without preceding shock. The patient was treated with immunosuppressants for myasthenia gravis. Patients 6 and 7 experienced intracranial bleeding. Patient 9 died of pulmonary embolism after prolonged ventilation for dengue encephalitis. Conclusions Prolonged shock, fluid overload and acute liver failure were common causes of dengue related deaths, in our study. Fluid overload occurred when vigorous crystalloid resuscitation was continued in patients who were poorly responding. A prompt switch to colloids or blood could have prevented overload. Patients who were in shock for a prolonged period become unresponsive to fluid resuscitation. How to manage dengue in patients who take anti-inflammatory drugs, immunomodulators, or antiplatelets is not known. Balancing the bleeding risk of dengue in patients predisposed to bleeding or thrombosis is a challenge.