SHOCK SYNOPSIS MAY 2025

ADJUNCTIVE VASOPRESSORS AND SHORT-TERM MORTALITY IN ADULTS WITH SEPTIC SHOCK: A SYSTEMATIC REVIEW AND META-ANALYSIS Adjunctive vasopressors are commonly added to norepinephrine in septic shock, but the effectiveness of this approach is unclear, and treatment recommendations are based on indirect evidence. Bauer et al. (pp. 668–676, DOI: 10.1097/SHK.0000000000002558) conducted a systematic review and meta-analysis to test the hypothesis that adjunctive vasopressors would improve outcomes in adult patients with sepsis. Data from seventeen randomized clinical trials that included 3,813 participants showed that adjunctive vasopressor administration may lower risk for short-term mortality compared with standard care vasopressors alone in adults with septic shock. However, evidence certainty was low due to risk of bias and imprecision. TRAUMA AND THE ENTEROCYTE: DISTURBANCE OF COMMUNICATION AND DELINEATION When trauma and hemorrhage occur, the intestine can experience significant damage, leading to a disruption in its barrier function. The comprehensive review by Meisen et al. (pp. 677–687, DOI: 10.1097/SHK.0000000000002564) explores the impact of diverse trauma patterns, including hemorrhagic shock, on the morphology and function of the intestine. A focus is set on mechanisms underlying intestinal barrier disruption caused by direct and remote trauma, alongside the associated intra- and intercellular miscommunication and metabolic changes in the enterocyte. Furthermore, therapeutic strategies aiming to reduce posttraumatic intestinal injury are examined across various species, providing an outlook on potential research directions and clinical translation. OPTIMAL PAO2 IS 130‐160 MMHG IN THE FIRST WEEK FOR SEPSIS PATIENTS IN ICU: A RETROSPECTIVE COHORT STUDY BASED ON MIMIC-IV DATABASE Oxygen therapy is often required to prevent and/or ameliorate hypoxemia and tissue hypoxia in sepsis patients. However, the optimal range of PaO2 remains controversial and many clinical studies have reported conflicting data. In the study by Chen et al. (pp. 688–694), the authors utilized a large, critical care database (Medical Information Mart for Intensive Care IV [MIMIC-IV]) and explored the association between different levels of PaO2 exposure over time and the 28-day mortality of sepsis patients. The authors observed that maintaining PaO2 levels within the range of ≥130 mmHg and ≤160 mmHg was crucial during the first week of ICU admission for sepsis patients. High-risk PaO2 exposure outside this range was identified as a risk factor for 28-day mortality after ICU admission. THE EFFICACY OF COAGULATION FACTOR CONCENTRATES IN THE MANAGEMENT OF PATIENTS WITH TRAUMA-INDUCED COAGULOPATHY: A SYSTEMATIC REVIEW AND META-ANALYSIS Transfusion and administration of blood component products are vital for trauma patients with uncontrolled bleeding. The article by Itagaki et al. (pp. 695–705, DOI: 10.1097/SHK.0000000000002534) provides a systematic review and meta-analysis into the safety and efficacy of coagulation factor concentrates (fibrinogen concentrate, prothrombin coagulation cofactor and their combination) for trauma-induced coagulopathy. The authors found no significant reduction in mortality but reductions in transfusion needs and complications. The study also highlights considerable variability in the definitions of trauma-induced coagulopathy, which complicates comparability and underscores the need for standardized criteria. A CLINICAL PREDICTION MODEL FOR SHORT-TERM PROGNOSIS IN PATIENTS WITH NON-ACUTE MYOCARDIAL INFARCTION-RELATED CARDIOGENIC SHOCK Patients with non-acute myocardial infarction (non-AMI) related cardiogenic shock (CS) differ from those with acute myocardial infarction (AMI)-complicated CS in terms of management, complications and outcomes. Wang et al. (pp. 706–713, DOI: 10.1097/SHK.0000000000002535) utilized two critical care database (Medical Information Mart for Intensive Care III [MIMIC-III] and MIMIC-IV) and constructed a nomogram for predicting in-hospital mortality. The authors demonstrated that the nomogram demonstrated good performance in short-term prognostic prediction and risk stratification, thus suggesting that this tool may support early decision making and timely intervention for patients with non-AMI complicated CS. MONOCYTES AND B CELLS MEDIATE ALTERATIONS IN THE GENETIC ASSOCIATION BETWEEN PLATELETS AND SEPSIS VIA CLEC SIGNALING PATHWAY Blood system dysfunction plays a significant role in the onset and progression of sepsis with the platelet abnormalities being particularly common. Yang et al. (pp. 714–722, DOI: 10.1097/SHK.0000000000002547), employed mendelian randomization studies and cell-cell communication analyses and identified an inverse genetic association between the platelets and sepsis indicating a protective effect of platelets in sepsis. The authors also report that monocytes and B cells are key mediators of this genetic association by regulating the platelets via the CLEC pathway. INCREASED CIRCULATORY KREBS CYCLE METABOLITES IN SEPSIS IS ASSOCIATED WITH INCREASED INTERLEUKIN-6 RELEASE AND WORSE SURVIVAL Elevated levels of circulatory Krebs cycle metabolites have been described in patients with sepsis, suggesting that they could potentially serve as biomarkers of disease progression. Chung et al. (pp. 723–732, DOI: 10.1097/SHK.0000000000002550) conducted a multicenter prospective study in adult patients with sepsis and found that plasma Krebs cycle metabolites were significantly correlated with circulatory IL-6 levels in sepsis. Particularly, plasma levels of α-ketoglutarate, fumarate, and malate were significantly associated with increased 28-day mortality independent of SOFA scores. The authors, therefore, suggest that Krebs cycle metabolites may be used as valid sepsis biomarkers to enhance prognostic evaluation when applied with the SOFA scores. SEX DIFFERENCES IN SEPSIS-RELATED ACUTE RESPIRATORY DISTRESS SYNDROME AND OTHER SHORT-TERM OUTCOMES AMONG CRITICALLY ILL PATIENTS WITH SEPSIS: A RETROSPECTIVE STUDY IN CHINA The evidence of sex disparity in acute respiratory distress syndrome (ARDS) is scarce and varies widely. By conducting a retrospective observational study, Zhao et al. (pp. 733–742, DOI: 10.1097/SHK.0000000000002555) aimed to determine the effect of sex on the sepsis-related ARDS and other short-term outcomes in critically ill patients with sepsis. In this study, male sex was identified as an independent risk factor for sepsis-related ARDS and in-hospital mortality. Interestingly, a sustained protective effect against acute lung injury was observed in female patients with sepsis and extended into the postmenopausal period. SEASONAL DIFFERENCES IN BURN INJURIES AND OUTCOMES AMONG ADULTS AND OLDER ADULTS AT A CANADIAN PROVINCIAL BURN CENTER Burn injuries pose a significant public health concern. Hutter et al. (pp. 743–749, DOI: 10.1097/SHK.0000000000002556) conducted a retrospective single-center cohort study and examined burn injury admission patterns and outcomes of hospitalized adult (18–59 years) and older adult burn patients (≥60 years) to identify targetable prevention measures and effective resource allocation. This study, located at a provincial burn center in Ontario, Canada, revealed that burn incidence peaked in Summer, with younger patients and more extensive burns compared to Winter. While hospitalization length per % total body surface area was shorter in Summer, mortality rates remained consistent across seasons. AKAP1-STABILIZED TIMP-4 ATTENUATES ANG-II-INDUCED OXIDATIVE STRESS AND INFLAMMATION IN VASCULAR SMOOTH MUSCLE CELLS BY INACTIVATING THE NF-ΚB SIGNALING Oxidative stress and inflammation are key factors contributing to the complex pathogenesis of abdominal aortic aneurysm (AAA). The study by Han et al. (pp. 750–759, DOI: 10.1097/SHK.0000000000002557) used an in vitro model of angiotensin II (Ang-II)-stimulated human vascular smooth muscle cells and demonstrated that Ang-II caused oxidative stress and inflammation through downregulation of both the tissue inhibitor of metalloproteinases-4 (TIMP-4) and the A-kinase anchoring protein 1 (AKAP1). Comparative analyses confirmed that TIMP-4 and AKAP1 levels were downregulated in tissues and serum of patients with AAA, further supporting the role of these factors in vascular damage. MORTALITY OF SEPTIC SHOCK SECONDARY TO PEDIATRIC PRIMARY PERITONITIS PREDICTED BY RESPIRATORY QUOTIENT COMBINED WITH LACTATE: A SURVEY FROM TWO CHILDREN’S HOSPITALS IN NORTHWEST CHINA Early detection of low perfusion and appropriate resuscitation are critical components in the management of patients with septic shock. The retrospective study by Wang et al. (pp. 760–766, DOI: 10.1097/SHK.0000000000002559) identified risk factors for the prognosis of septic shock secondary to pediatric primary peritonitis through a large analysis of metabolic-related biomarkers. The authors reported that respiratory quotient and lactate were independent prognostic factors for septic shock secondary to pediatric primary peritonitis. PTP1B AND ZONULIN FAILED TO PREDICT THE MODIFICATION OF MUSCLE MASS IN CRITICALLY ILL PATIENTS WITH SEPTIC SHOCK Proteolysis is one of the causes of loss of lean body mass. The study by Lemaitre et al. (pp. 767–773, DOI: 10.1097/SHK.0000000000002561) investigates the relationship between Protein-Tyrosine Phosphatase 1B (PTP1B), zonulin levels, and body composition in patients with septic shock. The results show a decrease in quadriceps muscle area between day 1 and day 4, but no significant correlation between PTP1B, zonulin levels, and muscle mass or fat-free mass. The study confirms that early muscle loss is a prognostic factor for mortality, but no connections were found between PTP1B, zonulin, and mortality outcomes. NAT10 PROMOTES PYROPTOSIS AND PANCREATIC INJURY OF SEVERE ACUTE PANCREATITIS THROUGH AC4C MODIFICATION OF NLRP3 Pyroptosis has been shown to promote the progression of severe acute pancreatitis. Using an in vivo rat model of pancreatitis and in vitro pancreatic exocrine cells, Gao et al. (pp. 774–780, DOI: 10.1097/SHK.0000000000002551) provide insights into the regulatory function of N-acetyltransferase 10 (NAT10) in cell death. The authors demonstrated that NAT10 is a key regulator responsible for macrophage NLRP3 inflammasome. Of importance, knockdown of NAT10 markedly ameliorated pancreatic injury, further supporting the pathological role of this enzyme. CLOSED-LOOP VENTILATION AND OXYGENATION WITH DECISION SUPPORT FLUID RESUSCITATION TO TREAT MAJOR BURN INJURY WITH SMOKE INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME Mechanical ventilation is an important measure of respiratory support for patients with acute respiratory distress syndrome. The study by Kakizaki et al. (pp. 781–787, DOI: 10.1097/SHK.0000000000002552) evaluated the efficacy of a closed-loop adaptive support ventilation system that automatically adjusts FiO2, PEEP, and ventilation, combined with urine-output–guided fluid resuscitation in burn and inhalation lung injury. By using a sheep model with combined burn and smoke inhalation, the authors demonstrated that the closed-loop group had better static lung compliance, lower driving pressure, and improved survival than a control group with standard support ventilation at 48 h despite a greater net fluid balance. ENDOTHELIAL-SPECIFIC KNOCKOUT OF THE SCRAMBLASE TMEM16F IMPAIRS IN VIVO CLOT FORMATION Circulating levels of extracellular histones are associated with endothelial damage, coagulopathy, and poor clinical outcomes after trauma. This study by Bonson et al. (pp. 788–795, DOI: 10.1097/SHK.0000000000002553) investigated whether the calcium-dependent phospholipid scramblase TMEM16F may mediate coagulopathy and endothelial damage associated with circulating extracellular histones after traumatic injury. The authors demonstrated that pharmacological inhibition of TMEM16F prevents histone-driven calcium oscillations in cultured endothelial cells. Moreover, endothelial-specific TMEM16F ablation in a mouse model of inferior vena cava stenosis resulted in a coagulopathic phenotype, with increased bleeding times and reduced thrombus formation. PLASMA UTILIZATION EXACERBATES RENAL CORTEX INFLAMMATION IN A RODENT MODEL OF HEMORRHAGIC SHOCK AND RESUSCITATION Resuscitation strategies in the management of traumatic hemorrhagic shock also include the use of fresh frozen plasma. Using an in vivo rodent model of hemorrhagic shock, Risinger et al. (pp. 796–803, DOI: 10.1097/SHK.0000000000002563) provide insights into the implications of fresh frozen plasma on renal physiology. The authors hypothesized that plasma resuscitation (compared to crystalloid) would improve intra-renal blood flow and reduce renal inflammation. The results show that plasma resuscitation did not enhance macro-circulatory blood flow within the kidney and exacerbated inflammatory signaling and downstream leukocyte infiltration into the renal cortex. FACTORS THAT PREDICT HYPOTENSION AFTER INDUCTION OF GENERAL ANESTHESIA IN ELDERLY PATIENTS – LETTER TO THE EDITOR In the letter to the editor, Wang (pp. 804–804) comments on the recent study by Wan et al. (Shock 2024 Nov. 11, DOI: 10.1097/SHK.0000000000002554). Wang praises the promising findings on reliable predictors of hypotension after the induction of general anesthesia in elderly patients but also highlights the need for careful consideration of statistical methods and further validation in larger cohorts.

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