Effect of anisodamine hydrobromide on improving early microcirculation disturbance in septic shock patients

Effect of anisodamine hydrobromide on improving early microcirculation disturbance in septic shock patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of anisodamine hydrobromide on improving early microcirculation disturbance in septic shock patients Xiaoxu Ding, Liwei Yan, Qi Yang, Xin Zhang, Zhanbiao Yu, Hao Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8704388/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract BACKGROUND Septic shock, prevalent in critical care medicine, poses significant treatment challenges and high mortality rates. Its pathogenesis involves an inflammatory cytokine storm and microcirculatory dysfunction, potentially leading to fatal multiple organ failure. Microcirculation alterations during septic shock critically impact patient outcomes. Anisodamine hydrobromide, a commonly used anticholinergic, mitigates oxidative stress and modulates cell apoptosis, notably enhancing microcirculation by targeting cholinergic receptors. This study investigates the efficacy of anisodamine hydrobromide in ameliorating microcirculatory disorders in septic shock patients. Methods This article collects 72 cases of patients with septic shock from the Department of Critical Care Medicine, Affiliated Hospital of Hebei University from 2020 to 2024. Participants were assigned to either a treatment group or a control group based on the administration of anisodamine hydrobromide. Data on heart rate, mean arterial pressure (MAP), blood lactate (LAC) levels, peripheral blood perfusion index (PI), and mottling scores were collected at 0, 6, 24, and 48 hours post-admission. Additionally, the 28-day mortality rate and progression from acral cyanosis to acral necrosis were assessed. Statistical analysis was conducted to compare differences in these indices between the groups. Results No statistically significant difference was observed in 28-day mortality between the treatment and control groups (14% vs. 16%; p = 0.86). Norepinephrine dosage also showed no significant difference. Heart rates at 6 and 24 hours post-treatment were statistically similar; however, at 48 hours, the treatment group exhibited a significantly lower heart rate than the control group. ScvO2 and Pcv-aCO2 levels did not differ significantly between groups at any time point (all p > 0.05). Comparison of microcirculatory oxygen metabolism indicators between the groups: The treatment group exhibited significant improvements in lactate and PI compared to the control group (P <0.05). At 6 and 24 hours post-treatment, the SMS scores were lower in the treatment group, though no significant difference was observed at 48 hours. CRT showed no difference at 6 hours, but the treatment group demonstrated significant improvement at 24 and 48 hours (P > 0.05). No statistically significant difference was found in the progression from acral cyanosis to acral necrosis between the groups. Conclusion The standardized treatment of septic shock, when combined with anisodamine hydrobromide infusion, enhances early microcirculation indicators in septic shock patients. Anisodamine hydrobromide Septic shock Microcirculation disorder Blood lactic acid (LAC) Peripheral perfusion index (PI) Mottling score Acral cyanosis Acral necrosis Figures Figure 1 Introduction Septic shock is characterized by sepsis with severe circulatory and cellular metabolic dysfunctions. The infection initiates an innate immune response, activating immune cells like mononuclear macrophages to release inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, and IL-6. Normally, the body’s anti-inflammatory mechanisms maintain equilibrium, but in septic shock, the inflammatory response becomes excessive and persistent, disrupting this balance and causing tissue damage. Inflammatory mediators harm vascular endothelial cells, increase vascular permeability, and lead to plasma exudation into tissue spaces, reducing effective circulating blood volume. Concurrently, vasomotor dysfunction results in abnormal vasodilation and microthrombus formation, impairing blood perfusion and depriving tissues and organs of adequate oxygen and nutrients [1] . Microcirculatory dysfunction is pivotal in the development of tissue hypoxia and organ failure during sepsis [2] . Despite achieving macro-hemodynamic resuscitation targets, microvascular perfusion alterations often persist. These microcirculatory issues intensify tissue hypoxia, shifting energy metabolism from aerobic to anaerobic, resulting in lactic acid accumulation and acidosis. Septic shock frequently involves decreased effective volume, leading to peripheral circulatory failure. Numerous studies have focused on evaluating peripheral circulation in shock treatment. [3] . In septic shock, peripheral vasoconstriction prioritizes blood flow to vital organs, reducing the perfusion index (PI). The extent of PI reduction correlates with shock severity. Research indicates that lower PI values are associated with severe microcirculatory disorders, such as poor skin perfusion, serving as an early indicator and severity assessment tool for shock. The presence of mottled skin during an initial patient assessment is a strong indicator of critical illness, often signaling hypoxia and blood stasis in terminal vessels. The mottling score serves as a semi-quantitative index for evaluating the severity of sepsis [4] . Elucidating the pathophysiological basis of the mottling score enhances its utility in assessing microcirculation. Bourcier's vascular reactivity tests revealed that patients with mottled skin frequently exhibit endothelial dysfunction [5] . Additionally, some researchers suggest that coagulation cascade activation and vasoconstriction, triggered by heightened sympathetic stress, contribute to mottling [6] . The primary pathophysiological mechanism of septic shock is microcirculatory dysfunction, leading to tissue hypoxia, organ dysfunction, and potentially life-threatening conditions. This can be viewed as a severe endothelial dysfunction syndrome. Infection triggers reversible or irreversible microcirculatory damage, significantly contributing to multiple organ failure [7] . Thus, regulating the inflammatory response and repairing endothelial damage are crucial in treating septic shock. Anisodamine hydrobromide has demonstrated efficacy in enhancing microcirculation and mitigating reperfusion injury by reducing oxidative stress, inhibiting apoptosis, alleviating inflammation, and activating the cholinergic anti-inflammatory pathway [8][9] . The current research on anisodamine for treating septic shock remains inadequate. Studies have not demonstrated that anisodamine reduces in-hospital mortality among critically ill adults with septic shock in intensive care [10] . Consequently, we conducted a randomized controlled trial focusing on microcirculation indicators, including blood lactic acid levels, peripheral perfusion index, mottling score, and the progression of acral cyanosis to necrosis. This trial aims to assess whether anisodamine hydrobromide can enhance microcirculation. 1. Data and methods 1.1 General Data: Clinical data from 72 septic shock patients admitted to the Department of Critical Care Medicine at the Affiliated Hospital of Hebei University between January 2024 and June 2025 were analyzed. Of these, 41 patients treated with anisodamine hydrobromide constituted the experimental group, while 31 untreated patients formed the control group. The mean age was 64 ± 10 years. Predominant conditions included severe pneumonia, urinary tract infections, enterogenic infections, and postoperative intra-abdominal infections. 1.2 Inclusion Criteria: ① Confirmed infection site. ② Systolic blood pressure (SBP) below 90 mmHg, necessitating vasopressors for stabilization. ③ Blood lactate levels exceeding 2 mmol/L. 1.3 Exclusion criteria: Patients younger than 18 years of age, pregnant women and patients with known peripheral vascular disease (e.g. peripheral arterial occlusive disease, vasculitis) were excluded. 1.4 Grouping Methods: Patients with septic shock were divided into two groups based on the administration of anisodamine hydrobromide. Both groups received standard septic shock treatment, including fluid resuscitation, vasopressors, empirical antibiotics, and organ support. In the experimental group, anisodamine hydrobromide was delivered via pump. The initial intravenous bolus was 0.5 mg/kg, with a minimum of 20 mg and a maximum of 40 mg. The maintenance dose ranged from .02 to .1 mg/kg/h, adjusted by the treating physician according to vital signs, lactate levels, and adverse reactions, with a daily maximum of 200 mg. Drug withdrawal criteria included: 1) recovery from shock (normal serum lactate levels and cessation of vasopressors); 2) unresolved drug-related complications despite symptomatic treatment (e.g., arrhythmia, allergic reaction, intestinal obstruction); 3) patient death. 1.5 Methods: A central venous catheter was inserted via the internal jugular or subclavian vein to simultaneously collect central venous and peripheral arterial blood for gas analysis. Indicators measured at admission and 12, 24, and 48 hours post-treatment included central venous oxygen saturation (ScvO₂), central venous partial pressure of carbon dioxide (PcvCO₂), peripheral arterial blood lactate (Lac), arterial partial pressure of carbon dioxide, pulse perfusion index (PI), capillary refill time (CRT), and skin mottling score (SMS). Statistical differences in these indicators, 28-day mortality, and the number of patients with acral cyanosis or progressing to acral necrosis were compared between the two groups. 1.6 Microcirculation monitoring indicators: Skin mottling score (SMS) was assessed using the criteria by Ait-Oufella et al. to evaluate peripheral microcirculatory perfusion. Capillary refill time (CRT) involved raising the patient's right index finger to heart level and pressing the fingertip with a glass slide until blanching occurred. After 10 seconds, the slide was removed, and the time for color return was recorded with a stopwatch; this process was repeated twice for an average. A CRT of ≥ 3 seconds indicated microcirculatory impairment. Pulse perfusion index (PI) was measured using a Mindray pulse oximetry monitor, with the middle finger as the consistent measurement site. 1.7 Statistical Methods: Statistical analyses were conducted using SPSS software. Non-normally distributed measurement data were reported as medians with interquartile ranges Q2 (Q1, Q3). Group comparisons employed the Mann-Whitney U test, while paired samples with non-normal distributions were analyzed using the Wilcoxon signed-rank test. Binary variable comparisons between two groups utilized the Pearson chi-square test. Statistical significance was set at P < .05. Survival curves for 28-day survival trends were generated using the Kaplan-Meier method, and the Fine-Gray test assessed differences in extremity necrosis risk between the groups. 2. Resuts 2.1 Participants Baseline characteristics of the patient groups: From the Department of Critical Care Medicine at the Affiliated Hospital of Hebei University, 85 patients were initially screened. Exclusions included 2 patients who died within 6 hours of admission, 2 with intestinal obstruction, 5 with an ICU stay exceeding 24 hours at enrollment, 1 with glaucoma, and 3 in the acute phase of cerebral hemorrhage. Ultimately, 72 patients were included: 41 in the treatment group and 31 in the control group(Table 1 ). All patients were on mechanical ventilation; 46 underwent CRRT, and 2 received ECMO. In the treatment group, anisodamine hydrobromide was administered for an average of 3.1 days. Table 1 Baseline characteristics of control and treatment groups Variables Total (n = 72) Control (n = 31) Treated (n = 41) Age (years), Median (Q1, Q3) 67(56,75) 67(54,76) 68(60,71) Gender, male n (%) 39(55%) 21(51%) 18(58%) Disease n(%) Craniocerebral injury 1(1.39%) 1(2.44%) 0(0.00%) Intestinal perforation 3(4.17%) 3(7.32%) 0(0.00%) Pneumonia 30(41.67%) 16(39.02%) 14(45.16%) Cholangitis 5(6.94%) 3(7.32%) 2(6.45%) Intestinal necrosis 1(1.39%) 1(2.44%) 0(0.00%) Intestinal infection 2(2.78%) 1(2.44%) 1(3.23%) Urinary tract infection 6(8.33%) 3(7.32%) 3(9.68%) Gastric cancer 1(1.39%) 1(2.44%) 0(0.00%) Abdominal infection 1(1.39%) 1(2.44%) 0(0.00%) Gastric perforation 4(5.56%) 3(7.32%) 1(3.23%) Uterine perforation 1(1.39%) 1(2.44%) 0(0.00%) Skin and soft tissue infection 2(2.78%) 1(2.44%) 1(3.23%) Appendicitis 1(1.39%) 1(2.44%) 0(0.00%) Liver abscess 2(2.78%) 1(2.44%) 1(3.23%) Infective endocarditis 1(1.39%) 1(2.44%) 0(0.00%) Abdominal trauma 1(1.39%) 1(2.44%) 0(0.00%) Intestinal tumor 1(1.39%) 0(0.00%) 1(3.23%) Leukemia 1(1.39%) 0(0.00%) 1(3.23%) COPD 3(4.17%) 1(2.44%) 2(6.45%) Pancreatitis 3(4.17%) 1(2.44%) 2(6.45%) Intracranial infection 1(1.39%) 0(0.00%) 1(3.23%) Peritonsillar inflammation 1(1.39%) 0(0.00%) 1(3.23%) Main infection site n(%) Lung n(%) 35(48.61%) 19(46.34%) 16(51.61%) Biliary system n(%) 5(6.94%) 3(7.32%) 2(6.45%) Abdominal cavity n(%) 16(22.22%) 12(29.27%) 4(12.90%) Intracranial n(%) 1(1.39%) 0(0.00%) 1(3.23%) Blood n(%) 3(4.17%) 1(2.44%) 2(6.45%) Endocardium n(%) 1(1.39%) 1(2.44%) 0(0.00%) Intestine n(%) 2(2.78%) 1(2.44%) 1(3.23%) Skin and soft tissue n(%) 2(2.78%) 1(2.44%) 1(3.23%) Urinary system n(%) 6(8.33%) 3(7.32%) 3(9.68%) Other sites n(%) 1(1.39%) 0(0.00%) 1(3.23%) Condition upon admission to the department SOFA(Q1、Q3) 12(12,14) 13(12,14) 12(12,15) APEACHii score (Q1, Q3) 14(15,16) 13(15,16) 14(15,16) Note:Both patient groups received septic shock treatment according to the Sepsis-3 Guidelines bundle. The control group additionally received an intravenous infusion of anisodamine hydrobromide alongside standard treatment. Lac denotes blood lactate, ScvO2 central venous oxygen saturation, PcCO2 (v-a) the central venous-arterial carbon dioxide partial pressure difference, PI the pulse perfusion index, SMS the skin mottling score, and CRT the capillary refill time. 2.2 Comparison of mortality between treatment and control groups The in-hospital mortality rate for the treatment group was marginally lower than that of the control group, though the difference was not statistically significant (14% vs. 16%; p = .86). The log-rank test of the Kaplan-Meier survival curves indicated no significant survival difference between the groups (Fig. 1 ). 2.3 Comparison of clinical indicators between the treatment group and the control group No significant difference in 28-day mortality was observed between the patient groups. Norepinephrine dosage within 48 hours post-treatment and heart rate at 6 and 4 hours post-treatment showed no significant differences between the groups. However, at 48 hours, the treatment group exhibited a statistically significant decrease in heart rate compared to the control group. ScvO₂ and Pcv-aCO₂ levels showed no significant differences across all time points (P > 0.05). In terms of microcirculatory oxygen metabolism, lactic acid and PI levels significantly improved in the treatment group compared to the control group (P <0.05). SMS scores were lower in the treatment group at 6 and 24 hours post-treatment, with no notable difference at 48 hours. Conversely, CRT scores showed no difference at 6 hours but significantly improved in the treatment group at 24 and 48 hours (P <0.05) (Table 2 ).. Regarding the comparison of oxygen metabolism indicators in the microcirculation between the two groups, levels of lactic acid and perfusion index (PI) were significantly improved in the treatment group compared to the control group (P > 0.05). The Sequential Organ Failure Assessment (SOFA) scores in the treatment group were lower than those in the control group at 6 hours and 24 hours post-treatment, with no significant difference between the groups at 48 hours. Conversely, when comparing the groups using the Capillary Refill Time (CRT) parameter, there was no distinction at 6 hours, but significant improvement was observed in the treatment group at 24 hours and 48 hours (P > 0.05) (Table 2 ). Table 2 Comparison of primary and secondary clinical outcomes between treatment and control groups Variables Total ( n = 72) Control ( n = 31) Treated ( n = 41) p value 28-day mortality rate 11(15%) 6(14%) 5(16%) 0.860 Median NE dosage Median(Q1、Q3) 0h 0.5(0.4,0.65) 0.5(0.4,0.6) 0.5(0.4,0.675) 0.880 6h 0.4(0.4,0.5) 0.4(0.3,0.4) 0.5(0.4,0.6) 0.122 24h 0.3(0.3,0.4) 0.3(0.2,0.3) 0.4(0.3,0.4) 0.271 48h 0.1(0.1,0.2) 0.1(0.1,0.1) 0.2(0.2,0.2) 0.101 heart rate median(Q1、Q3) 0h 98(84.5,109.5) 98(78,110) 99(88,109) 0.350 6h 86.5(75,98) 78(68,95) 87(78,98) 0.178 24h 78(67,86.5) 76(67,86) 78(68.5,87) 0.218 48h 69.5(65.75,78.5) 68(65,76) 78(67,89) 0.005 LAC median(Q1、Q3) 0h 3.35(2.75,4.4) 3.2(2.8,4.7) 3.4(2.6,3.4) 0.945 6h 2.1(1.6,3.1) 1.4(1.3,1.6) 3.1(2.1,4.2) 0.000 24h 1.55(1.375,2.5) 1.4(1.3,1.6) 2.5(1.55,4.225) 0.000 48h 1.35(1.1,2.05) 1.1(1,1.3) 2.1(1.5,2.1) 0.000 ScVO2% median(Q1、Q3) 0h 58(54,65) 58(54,65) 57(54,65) 0.750 6h 64(57.75,65) 64(62,65) 63(56,65) 0.102 24h 65(61.75,67) 5(63,67) 64(58,68.75) 0.141 48h 67(63.75,69) 67(65,69) 68(62,72.75) 0.454 P(v-a)CO2 median(Q1、Q3) 0h 7(6,8) 7(6,8) 7(6,8.75) 0.754 6h 5(4,6) 5(5,6) 5(4,6) 0.053 24h 5(4,6) 5(4,5) 5(3.5,6) 0.500 48h 4(3,5) 4(4,5) 4(3,5) 0.326 Variables Total ( n = 72) Control ( n = 31) Treated ( n = 41) p value PI median(Q1、Q3) 0h 1.1(0.515,1.35) 1.1(0.5,1.4) 1.1(0.525,0.75) 0.954 6h 1.6(1.275,2.1) 1.7(1.5,2.3) 1.28(0.965,1.95) 0.020 24h 2.1(1.4,2.5) 2.4(2.1,3.1) 1.45(1.07,1.885) 0.000 48h 2.4(1.875,2.4) 2.7(2.4,3.2) 1.9(1.8,2.2) 0.000 SMS median(Q1、Q3) 0h 3(2,4) 3(3,4) 4(3,5) 0.199 6h 1.5(1,2) 1(1,2) 2(1.5,3) 0.001 24h 1(1,2) 1(1,1) 2(1,2) 0.014 48h 1(0,2) 0(0,1) 2(0,2) 0.057 CRT median(Q1、Q3) 0h 4(3,5) 4(3,5) 4(3,5) 0.341 6h 4(3,4.5) 4(3,5) 3(3,4) 0.708 24h 3(2,4) 3(2,4) 3(3,4) 0.010 48h 3(2,4) 2(2,4) 3(2.5,4) 0.021 2.4 Comparison of patients with acral cyanosis progressing to acral necrosis between the two groups. Table 3 details the incidence of acral cyanosis in each group. Group Number of cases Acrocyanosis No acral cyanosis Statistic P value Control 41 9(21.95%) 32(78.05) χ²=1.12 0.29 Treatment 31 10(32.26) 21(67.74) df = 1 - Total 72 19(26.39) 53(73.61) - - Table 4 Distribution of acral cyanosis events progressing to necrosis and mortality across two patient groups. Group Total Limb Necrosis Death (Competing event) Censored Control 10 2 (20.0%) 4 (40.0%) 4 (40.0%) Treatment 9 1 (11.1%) 4 (44.4%) 4 (44.4%) Table 5 Fine-Gray competing risks analysis results. Variable sHR 95% CI P value Treatment vs Control 0.51 0.07–3.48 0.49 sHR: Subdistribution Hazard Ratio Symmetric peripheral gangrene (SPG) is characterized by cyanosis and ecchymosis of the extremities, typically starting at the fingers and progressing proximally, potentially leading to necrosis, ulcers, and ultimately gangrene. Table 3 compares acrocyanosis occurrence between two patient groups. In the experimental group, 9 out of 41 cases (21.95%) exhibited acrocyanosis, whereas in the control group, 10 out of 31 cases (32.26%) showed this symptom. A chi-square test yielded X2 = 1.12, df = 1, and P = .29, indicating no statistically significant difference in acrocyanosis incidence between the groups. Table 4 details patient outcomes with acral cyanosis. In the control group, 2 out of 10 patients (20%) progressed to acral necrosis, 4 (40.%) died before necrosis could be observed, and 4 (40.%) did not develop necrosis. In the experimental group, 1 out of 9 patients (11.1%) progressed to acral necrosis, 4 (44.4%) died before necrosis observation, and 4 (44.4%) did not develop necrosis. The Fine-Gray competing risk model (Table 5 ) yielded a sub-distribution hazard ratio (sHR) of .51 (95% CI: .07–3.48) for the experimental group compared to the control, with a P-value of 0.49, indicating no significant difference in acral necrosis risk between the groups. 3. Discussion Advancements in septic shock treatments reveal that achieving macro-hemodynamic stability is merely a component of sepsis management; the primary objective is optimizing microvascular blood flow. Septic shock often disrupts "hemodynamic coherence," indicating a disconnect between systemic and microcirculatory responses [ 11 ] . Clinically, using high-dose vasoactive drugs to maintain mean arterial pressure (MAP) above 65 mmHg frequently results in extremity necrosis [ 12 ] . Effective organ and tissue perfusion necessitates optimizing microcirculatory regulation—targeting arterioles, capillaries, and venules—rather than solely maintaining blood pressure, which can lead to peripheral vascular occlusion [ 13 ] . Thus, identifying methods and drugs to enhance microcirculation is imperative. This study assessed anisodamine hydrobromide's impact on microcirculation and clinical outcomes. No significant difference in 28-day mortality was observed between the groups, likely due to the multifactorial nature of septic shock, which involves complex interactions such as multiple organ failure, gastrointestinal ischemia, and the adequacy of cardiopulmonary resuscitation [ 14 ] . While anisodamine hydrobromide enhances microcirculation, it may not mitigate other lethal risk factors like uncontrolled infection sources and organ failure. The "macrovasodilation and microvasoconstriction" seen in septic shock reflects pathological disparities in systemic inflammatory responses and vascular regulation across different vessel levels, influenced by vascular structure, regulatory mechanisms, and local microenvironment changes [ 15 ] . The tension in large blood vessels, such as the aorta, middle artery, and vein, is primarily influenced by neurohumoral regulation and systemic inflammatory mediators [ 16 ] . Infections activate immune cells to release inflammatory factors like TNF-α and IL-6, prompting cells in the liver, kidney, and intestine to produce substantial amounts of nitric oxide (NO) [ 17 ] . As a potent vasodilator, NO penetrates vascular smooth muscle cells, activating guanylate cyclase and increasing cGMP, which leads to smooth muscle relaxation. Research indicates that anisodamine hydrobromide's antishock effect is mediated by IL-10, and this effect is significantly reduced in IL-10-deficient mice [ 18 ] . However, not all septic shock patients exhibit elevated IL-10 levels; insufficient anti-inflammatory compensation can result in an excessive pro-inflammatory response, causing severe tissue damage. This impairs immune cell function, diminishes pathogen clearance, complicates infection control, and worsens prognosis. In such cases, the antishock efficacy of anisodamine hydrobromide is limited. The lack of statistical difference in norepinephrine (NE) dosage between the two groups within 48 hours post-treatment can be attributed to the regulation of large vessel tension primarily by sympathetic nerves (via α-adrenergic receptors), the renin-angiotensin system, and humoral factors like catecholamines and endothelin [ 19 ] . M-choline receptors are sparsely distributed on smooth muscle cells. Anisodamine hydrobromide, a selective M-choline receptor antagonist, primarily affects M-receptors on small vessel smooth muscle, alleviating spasms by counteracting acetylcholine and other vasoconstrictors. In contrast, its direct impact on large vessels such as the aorta, superior mesenteric artery, and renal artery is minimal due to the low density of M receptors, thus not significantly altering basal tension. Consequently, any improvement in blood pressure or reduction in blood pressure medication is negligible. Macrocirculatory parameters, such as central venous oxygen saturation (ScvO₂) and the central veno-arterial carbon dioxide gradient (Pcv-aCO₂), are often used to evaluate systemic oxygen metabolism and tissue perfusion [ 20 , 21 ] . In this study, no significant differences in ScvO₂ and Pcv-aCO₂ were observed between the treatment and control groups at any time point. This suggests that anisodamine hydrobromide primarily enhances microcirculation perfusion with minimal impact on systemic oxygen metabolism. Whole-body oxygen metabolism is influenced by factors such as respiratory function and hemoglobin levels. Following microcirculation improvement by anisodamine hydrobromide, noticeable changes in systemic oxygen metabolism may require extended time or complex physiological adjustments. In the microcirculation oxygen metabolism index, the lactic acid levels in the PI treatment group showed a significant improvement compared to the control group. Lactate is crucial for diagnosing and assessing septic shock [ 22 ] and serves as a vital marker of tissue hypoxia and anaerobic metabolism [ 23 ] . A reduction in lactate levels suggests that anisodamine hydrobromide effectively alleviates tissue hypoxia. This effect is attributed to anisodamine hydrobromide's ability to block M choline receptors on vascular smooth muscle, thereby alleviating microvasospasm (including arterioles, venules, and pre-capillary sphincters), stabilizing the endothelium, and inhibiting microthrombosis [ 24 , 25 ] . Enhancing microcirculatory blood flow improves tissue and organ oxygenation. Correcting tissue hypoxia mitigates anaerobic metabolism, thereby lowering lactic acid production and blood lactate levels. The perfusion index (PI), indicating local tissue blood flow, is calculated as the ratio of the pulse wave in pulsating to non-pulsating regions. While research on macrocirculatory stability in septic shock patients is well-established, microcirculation has emerged as a focal point of study. It is recognized that microcirculatory failure is a fundamental pathological feature of septic shock, with clinical challenges often arising from the decoupling of macro- and microcirculation [ 26 ] . During septic shock, the release of inflammatory mediators like TNF-α and IL-6, along with sympathetic excitation and vasoactive substances such as catecholamines and angiotensin, induces persistent spasms and contractions in systemic microvessels, particularly arterioles and precapillary sphincters. This phenomenon effectively "blocks" the microcirculation pathway entrance, hindering blood flow into the capillary bed and leading to tissue ischemia and hypoxia [ 27 ] . The study's observed improvement in PI underscores the regulatory impact of anisodamine hydrobromide on microcirculation, enhancing microvascular perfusion and tissue oxygenation. These findings indicate that anisodamine hydrobromide significantly improves microcirculatory oxygen metabolism, playing a crucial role in alleviating tissue hypoxia in septic shock patients. The speckle score (SMS) was employed as a specific index to assess peripheral microcirculation disorders in shock severity [ 28 ] . Scores for the treatment group were significantly lower than those of the control group at 6 and 24 hours post-treatment, with no significant difference observed at 48 hours. The speckle score quantifies the extent and duration of skin speckle, directly reflecting the perfusion state of skin microcirculation. The early-stage decrease in scores suggests that anisodamine hydrobromide rapidly restores microcirculation perfusion in peripheral tissues, such as skin, by alleviating arteriolar spasm and improving capillary blood flow. However, the score difference diminished at 48 hours, possibly due to improved microcirculation in the control group from overall treatment measures like fluid resuscitation and antibiotic intervention. Additionally, the speckle score's sensitivity may decline in the later shock stages, as vascular endothelial damage from prolonged hypoxia necessitates more complex repair mechanisms [ 29 ] . Distal gangrene in septic shock patients typically signals severe hypotension or elevated vasoconstrictor drug use, manifesting symmetrically or locally in fingers, toes, and potentially extending to feet or legs [ 30 ] . Unlike large artery occlusion, SPG arises from microvascular dysfunction and small vessel thrombosis [ 31 ] . This pathophysiology likely stems from a significant imbalance between procoagulant and anticoagulant factors within the tissue vascular bed, leading to microthrombosis [32、33] . Anisodamine hydrobromide theoretically inhibits microthrombosis, yet the study failed to confirm its efficacy in reversing acrocyanosis and necrosis. This may be due to acrocyanosis necrosis being the end-stage manifestation of microcirculation disorders, which involves not only microthrombosis but also factors like vascular endothelial injury, apoptosis, and metabolic failure from prolonged tissue ischemia. Anisodamine hydrobromide primarily acts by inhibiting thromboxane synthesis and improving early microcirculation blood flow. However, it is insufficient as a single intervention to halt necrosis driven by irreversible cellular damage and multifactorial tissue necrosis. Its impact on microcirculation is more apparent in hemodynamic measures, such as improved perfusion index (PI) and reduced lactate (LAC) levels. Nonetheless, acronecrosis results from long-term severe ischemia, and short-term hemodynamic improvements may not fully reverse ischemic tissue damage, thus inadequately reducing necrosis incidence. Additionally, the study's small sample size warrants consideration, suggesting the need for larger-scale research to delve deeper into this area. Anisodamine hydrobromide effectively enhances early microcirculation oxygen metabolism, reduces heart rate, and improves peripheral circulation in septic shock patients. While it did not significantly impact 28-day mortality, NE dosage, systemic oxygen metabolism, or limb necrosis improvement in this study, its efficacy in addressing microcirculation disorders remains notable. Future research should increase sample size, extend observation periods, and investigate the mechanisms and combined effects with other treatments to develop more effective strategies for septic shock management. Declarations Ethics approval and consent to participate This study was reviewed and approved by the Ethics Committee of The Affiliated Hospital of Hebei University (Approval No. HDFY-KY-2024-001). Informed consent was obtained from all individual participants included in the study. This study is not a clinical trial. Clinical trial number: not applicable. Consent for publication All participants provided informed consent for the publication of their anonymized data. Written informed consent for publication was obtained for this manuscript for any case details, images, or other potentially identifiable information. Funding This work was supported by the Baoding Science and Technology Bureau under Grant 2241ZF098. Author Contribution Xiaoxu Ding and Liwei Yan contributed equally to this work. X.D. and L.Y.: Conceptualization, Methodology, Investigation, Writing – Original Draft. Q.Y. and X.Z.: Formal analysis, Visualization, Writing – Review & Editing. Z.Y. and H.L.: Supervision, Funding acquisition, Project administration. All authors read and approved the final manuscript. Data Availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Due to privacy and ethical concerns, supporting data cannot be made openly available. Access requests will be assessed on a case-by-case basis in compliance with the approved ethical protocol. References De Backer D, Ricottilli F, Ospina-Tascón GA. Septic shock: a microcirculation disease. Curr Opin Anaesthesiol. 2021;34(2):85–91. doi: 10.1097/ACO.0000000000000957 Damiani E, Carsetti A, Casarotta E, Domizi R, Scorcella C, Donati A, Adrario E. Microcirculation-guided resuscitation in sepsis: the next frontier? Front Med (Lausanne). 2023;10:1212321. doi: 10.3389/fmed.2023.1212321 Hariri G, Joffre J, Leblanc G, Bonsey M, Lavillegrand JR, Urbina T, Guidet B, Maury E, Bakker J, Ait-Oufella H. Narrative review: clinical assessment of peripheral tissue perfusion in septic shock. Ann Intensive Care. 2019;9(1):37. doi: 10.1186/s13613-019-0511-1 Ait-Oufella H, Lemoinne S, Boelle PY, Galbois A, Baudel JL, Lemant J, Joffre J, Margetis D, Guidet B, Maury E, Offenstadt G. Mottling score predicts survival in septic shock. Intensive Care Med. 2011;37(5):801–7. doi: 10.1007/s00134-011-2163-y . Bourcier S, Joffre J, Dubée V, Preda G, Baudel JL, Bigé N, Leblanc G, Levy BI, Guidet B, Maury E, Ait-Oufella H. Marked regional endothelial dysfunction in mottled skin area in patients with severe infections. Crit Care. 2017;21(1):155. doi: 10.1186/s13054-017-1742-x . Lima A, Bakker J. Clinical assessment of peripheral circulation. 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Crit Care Med. 2000;28(8):2729–32. doi: 10.1097/00003246-200008000-00007 Driessen RGH, Heijnen NFL, Hulsewe RPMG, Holtkamp JWM, Winkens B, van de Poll MCG, van der Horst ICC, Bergmans DCJJ, Schnabel RM. Early ICU-mortality in sepsis - causes, influencing factors and variability in clinical judgement: a retrospective cohort study. Infect Dis (Lond). 2021;53(1):61–68. doi: 10.1080/23744235.2020.1821912 . De Backer D, Ricottilli F, Ospina-Tascón GA. Septic shock: a microcirculation disease. Curr Opin Anaesthesiol. 2021;34(2):85–91. doi: 10.1097/ACO.0000000000000957 Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet. 2005 Jan 1–7;365(9453):63–78. doi: 10.1016/S0140-6736(04)17667-8 Bultinck J, Sips P, Vakaet L, Brouckaert P, Cauwels A. Systemic NO production during (septic) shock depends on parenchymal and not on hematopoietic cells: in vivo iNOS expression pattern in (septic) shock. FASEB J. 2006;20(13):2363–5. doi: 10.1096/fj.06-5798fje Li Q, Lei H, Liu A, Yang Y, Su D, Liu X. The antishock effect of anisodamine requires the upregulation of α7 nicotine acetylcholine receptors by IL-10. Life Sci. 2011;89(11–12):395–401. doi: 10.1016/j.lfs.2011.07.008 Wieruszewski PM, Khanna AK. Vasopressor Choice and Timing in Vasodilatory Shock. Crit Care. 2022;26(1):76. doi: 10.1186/s13054-022-03911-7 Blasco V, Leone M, Textoris J, Visintini P, Albanèse J, Martin C. Oxymétrie veineuse: physiologie et implications thérapeutiques [Venous oximetry: physiology and therapeutic implications]. Ann Fr Anesth Reanim. 2008;27(1):74–82. French. doi: 10.1016/j.annfar.2007.10.031 Dubin A, Pozo MO, Hurtado J. Central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio as an indicator of tissue oxygenation: a narrative review. Rev Bras Ter Intensiva. 2020;32(1):115–122. doi: 10.5935/0103-507x.20200017 Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–10. doi: 10.1001/jama.2016.0287 BRODER G, WEIL MH. EXCESS LACTATE: AN INDEX OF REVERSIBILITY OF SHOCK IN HUMAN PATIENTS. Science. 1964;143(3613):1457–9. doi: 10.1126/science.143.3613.1457 Xiu RJ, Hammerschmidt DE, Coppo PA, Jacob HS. Anisodamine inhibits thromboxane synthesis, granulocyte aggregation, and platelet aggregation. A possible mechanism for its efficacy in bacteremic shock. JAMA. 1982;247(10):1458–60. doi: 10.1001/jama.247.10.1458 Du X, Liu H, Yue Y, Wu Q, Jiang W, Qiu Y, Zeng Y. Anisodamine Hydrobromide Protects Glycocalyx and Against the Lipopolysaccharide-Induced Increases in Microvascular Endothelial Layer Permeability and Nitric Oxide Production. Cardiovasc Eng Technol. 2021;12(1):91–100. doi: 10.1007/s13239-020-00486-8 Ince C, Mik EG. Microcirculatory and mitochondrial hypoxia in sepsis, shock, and resuscitation. J Appl Physiol (1985). 2016;120(2):226 – 35. doi: 10.1152/japplphysiol.00298.2015IF: 3.3 Q1. Epub 2015 Jun 11. PMID: 26066826. Vallet B. Endothelial cell dysfunction and abnormal tissue perfusion. Crit Care Med. 2002;30(5 Suppl):S229-34. doi: 10.1097/00003246-200205001-00010 . PMID: 12004241. Dumas G, Lavillegrand JR, Joffre J, Bigé N, de-Moura EB, Baudel JL, Chevret S, Guidet B, Maury E, Amorim F, Ait-Oufella H. Mottling score is a strong predictor of 14-day mortality in septic patients whatever vasopressor doses and other tissue perfusion parameters. Crit Care. 2019;23(1):211. doi: 10.1186/s13054-019-2496-4 . PMID: 31182133; PMCID: PMC6558704. Bourcier S, Joffre J, Dubée V, Preda G, Baudel JL, Bigé N, Leblanc G, Levy BI, Guidet B, Maury E, Ait-Oufella H. Marked regional endothelial dysfunction in mottled skin area in patients with severe infections. Crit Care. 2017;21(1):155. doi: 10.1186/s13054-017-1742-x . PMID: 28641580; PMCID: PMC5481873. Alhumam T, Alhumam AA, Alhumaidi I, Al Rajeh I, Alduhailan Y. Relationship Between Symmetrical Peripheral Gangrene Patients and Using Vasopressors in the Intensive Care Unit. Cureus. 2024;16(4):e58117. DOI: 10.7759/cureus.58117 . PMID: 38741803; PMCID: PMC11088959. Foead AI, Mathialagan A, Varadarajan R, Larvin M. Management of Symmetrical Peripheral Gangrene. Indian J Crit Care Med. 2018;22(12):870–874. doi: 10.4103/ijccm.IJCCM_379_18 . PMID: 30662227; PMCID: PMC6311972. Ghosh SK, Bandyopadhyay D. Symmetrical peripheral gangrene. Indian J Dermatol Venereol Leprol. 2011 Mar-Apr;77(2):244-8. doi: 10.4103/0378-6323.77481 . PMID: 21393969. Warkentin TE, Ning S. Symmetrical peripheral gangrene in critical illness. Transfus Apher Sci. 2021;60(2):103094. doi: 10.1016/j.transci.2021.103094 . Epub 2021 Feb 13. PMID: 33627309. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8704388","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":595162521,"identity":"9d40d918-72ab-453a-8b13-31923600ba34","order_by":0,"name":"Xiaoxu Ding","email":"","orcid":"","institution":"Affiliated Hospital of Hebei University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoxu","middleName":"","lastName":"Ding","suffix":""},{"id":595162522,"identity":"40adf96a-27b1-4bf5-9634-c181db823011","order_by":1,"name":"Liwei Yan","email":"","orcid":"","institution":"Affiliated Hospital of Hebei University","correspondingAuthor":false,"prefix":"","firstName":"Liwei","middleName":"","lastName":"Yan","suffix":""},{"id":595162523,"identity":"ebd604f9-6aad-45e1-8a16-bbe32ad98fec","order_by":2,"name":"Qi Yang","email":"","orcid":"","institution":"Affiliated Hospital of Hebei University","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Yang","suffix":""},{"id":595162524,"identity":"a465d252-0a1d-46b1-b8ee-fc69859ae659","order_by":3,"name":"Xin Zhang","email":"","orcid":"","institution":"Affiliated Hospital of Hebei University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Zhang","suffix":""},{"id":595162525,"identity":"9b27bbf4-de98-406d-9d1c-9bf51f587661","order_by":4,"name":"Zhanbiao Yu","email":"","orcid":"","institution":"Affiliated Hospital of Hebei University","correspondingAuthor":false,"prefix":"","firstName":"Zhanbiao","middleName":"","lastName":"Yu","suffix":""},{"id":595162526,"identity":"61490e8b-8ae2-4c46-8936-c62c685df197","order_by":5,"name":"Hao Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYBACAwYGxgMJBhL1/ewNIK4FUVoYDiRU2DDO7DkA4koQqYXhTBrjhhsJID4RWszZDx848LDtMLPBzedXN/wokGDgb+9OwKvFsict4UBi22E2yds5ZTd7gA6TOHN2A36HHcgxAGnh4budk3aDB6jFQCKXgJbzb8BaJBhunkm7+YcoLTeAtiScSTMQuMF+7DZxttx4lgAK5ATJnhy22zIGEjyE/XI++eDDHwYSCfzsx5/dfPPHRo6/vRe/FiTAYwAmiVUOAuwPSFE9CkbBKBgFIwgAADwrUZ+Cxvv+AAAAAElFTkSuQmCC","orcid":"","institution":"Affiliated Hospital of Hebei University","correspondingAuthor":true,"prefix":"","firstName":"Hao","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2026-01-27 00:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8704388/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8704388/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103258701,"identity":"bdf2ff16-ba61-4d41-ab6f-eb7ebbe84b11","added_by":"auto","created_at":"2026-02-23 17:32:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13686,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curve\u003c/p\u003e\n\u003cp\u003eNote: 1 represents treatment group and 2 represents control group.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8704388/v1/7cddabb5a7a860bfbc76d020.png"},{"id":106489001,"identity":"2e8125d5-9870-4d10-8d2d-9fc2e0ab682a","added_by":"auto","created_at":"2026-04-09 06:58:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":960399,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8704388/v1/28d2266f-9e48-40b4-9a42-42ee1628ab2f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of anisodamine hydrobromide on improving early microcirculation disturbance in septic shock patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSeptic shock is characterized by sepsis with severe circulatory and cellular metabolic dysfunctions. The infection initiates an innate immune response, activating immune cells like mononuclear macrophages to release inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, and IL-6. Normally, the body’s anti-inflammatory mechanisms maintain equilibrium, but in septic shock, the inflammatory response becomes excessive and persistent, disrupting this balance and causing tissue damage. Inflammatory mediators harm vascular endothelial cells, increase vascular permeability, and lead to plasma exudation into tissue spaces, reducing effective circulating blood volume. Concurrently, vasomotor dysfunction results in abnormal vasodilation and microthrombus formation, impairing blood perfusion and depriving tissues and organs of adequate oxygen and nutrients\u003csup\u003e[1]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eMicrocirculatory dysfunction is pivotal in the development of tissue hypoxia and organ failure during sepsis \u003csup\u003e[2]\u003c/sup\u003e. Despite achieving macro-hemodynamic resuscitation targets, microvascular perfusion alterations often persist. These microcirculatory issues intensify tissue hypoxia, shifting energy metabolism from aerobic to anaerobic, resulting in lactic acid accumulation and acidosis. Septic shock frequently involves decreased effective volume, leading to peripheral circulatory failure. Numerous studies have focused on evaluating peripheral circulation in shock treatment.\u003csup\u003e[3]\u003c/sup\u003e. In septic shock, peripheral vasoconstriction prioritizes blood flow to vital organs, reducing the perfusion index (PI). The extent of PI reduction correlates with shock severity. Research indicates that lower PI values are associated with severe microcirculatory disorders, such as poor skin perfusion, serving as an early indicator and severity assessment tool for shock.\u003c/p\u003e\n\u003cp\u003eThe presence of mottled skin during an initial patient assessment is a strong indicator of critical illness, often signaling hypoxia and blood stasis in terminal vessels. The mottling score serves as a semi-quantitative index for evaluating the severity of sepsis\u003csup\u003e\u0026nbsp;[4]\u003c/sup\u003e. Elucidating the pathophysiological basis of the mottling score enhances its utility in assessing microcirculation. Bourcier's vascular reactivity tests revealed that patients with mottled skin frequently exhibit endothelial dysfunction\u003csup\u003e\u0026nbsp;[5]\u003c/sup\u003e. Additionally, some researchers suggest that coagulation cascade activation and vasoconstriction, triggered by heightened sympathetic stress, contribute to mottling\u003csup\u003e\u0026nbsp;[6]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe primary pathophysiological mechanism of septic shock is microcirculatory dysfunction, leading to tissue hypoxia, organ dysfunction, and potentially life-threatening conditions. This can be viewed as a severe endothelial dysfunction syndrome. Infection triggers reversible or irreversible microcirculatory damage, significantly contributing to multiple organ failure\u003csup\u003e\u0026nbsp;[7]\u003c/sup\u003e. Thus, regulating the inflammatory response and repairing endothelial damage are crucial in treating septic shock. Anisodamine hydrobromide has demonstrated efficacy in enhancing microcirculation and mitigating reperfusion injury by reducing oxidative stress, inhibiting apoptosis, alleviating inflammation, and activating the cholinergic anti-inflammatory pathway \u003csup\u003e[8][9]\u003c/sup\u003e. The current research on anisodamine for treating septic shock remains inadequate. Studies have not demonstrated that anisodamine reduces in-hospital mortality among critically ill adults with septic shock in intensive care\u003csup\u003e\u0026nbsp;[10]\u003c/sup\u003e. Consequently, we conducted a randomized controlled trial focusing on microcirculation indicators, including blood lactic acid levels, peripheral perfusion index, mottling score, and the progression of acral cyanosis to necrosis. This trial aims to assess whether anisodamine hydrobromide can enhance microcirculation.\u003c/p\u003e"},{"header":"1. Data and methods","content":"\u003cp\u003e1.1 General Data: Clinical data from 72 septic shock patients admitted to the Department of Critical Care Medicine at the Affiliated Hospital of Hebei University between January 2024 and June 2025 were analyzed. Of these, 41 patients treated with anisodamine hydrobromide constituted the experimental group, while 31 untreated patients formed the control group. The mean age was 64\u0026thinsp;\u0026plusmn;\u0026thinsp;10 years. Predominant conditions included severe pneumonia, urinary tract infections, enterogenic infections, and postoperative intra-abdominal infections.\u003c/p\u003e\n\u003cp\u003e1.2 Inclusion Criteria: ① Confirmed infection site. ② Systolic blood pressure (SBP) below 90 mmHg, necessitating vasopressors for stabilization. ③ Blood lactate levels exceeding 2 mmol/L.\u003c/p\u003e\n\u003cp\u003e1.3 Exclusion criteria: Patients younger than 18 years of age, pregnant women and patients with known peripheral vascular disease (e.g. peripheral arterial occlusive disease, vasculitis) were excluded.\u003c/p\u003e\n\u003cp\u003e1.4 Grouping Methods: Patients with septic shock were divided into two groups based on the administration of anisodamine hydrobromide. Both groups received standard septic shock treatment, including fluid resuscitation, vasopressors, empirical antibiotics, and organ support. In the experimental group, anisodamine hydrobromide was delivered via pump. The initial intravenous bolus was 0.5 mg/kg, with a minimum of 20 mg and a maximum of 40 mg. The maintenance dose ranged from .02 to .1 mg/kg/h, adjusted by the treating physician according to vital signs, lactate levels, and adverse reactions, with a daily maximum of 200 mg. Drug withdrawal criteria included: 1) recovery from shock (normal serum lactate levels and cessation of vasopressors); 2) unresolved drug-related complications despite symptomatic treatment (e.g., arrhythmia, allergic reaction, intestinal obstruction); 3) patient death.\u003c/p\u003e\n\u003cp\u003e1.5 Methods: A central venous catheter was inserted via the internal jugular or subclavian vein to simultaneously collect central venous and peripheral arterial blood for gas analysis. Indicators measured at admission and 12, 24, and 48 hours post-treatment included central venous oxygen saturation (ScvO₂), central venous partial pressure of carbon dioxide (PcvCO₂), peripheral arterial blood lactate (Lac), arterial partial pressure of carbon dioxide, pulse perfusion index (PI), capillary refill time (CRT), and skin mottling score (SMS). Statistical differences in these indicators, 28-day mortality, and the number of patients with acral cyanosis or progressing to acral necrosis were compared between the two groups.\u003c/p\u003e\n\u003cp\u003e1.6 Microcirculation monitoring indicators: Skin mottling score (SMS) was assessed using the criteria by Ait-Oufella et al. to evaluate peripheral microcirculatory perfusion. Capillary refill time (CRT) involved raising the patient\u0026apos;s right index finger to heart level and pressing the fingertip with a glass slide until blanching occurred. After 10 seconds, the slide was removed, and the time for color return was recorded with a stopwatch; this process was repeated twice for an average. A CRT of \u0026ge;\u0026thinsp;3 seconds indicated microcirculatory impairment. Pulse perfusion index (PI) was measured using a Mindray pulse oximetry monitor, with the middle finger as the consistent measurement site.\u003c/p\u003e\n\u003cp\u003e1.7 Statistical Methods: Statistical analyses were conducted using SPSS software. Non-normally distributed measurement data were reported as medians with interquartile ranges Q2 (Q1, Q3). Group comparisons employed the Mann-Whitney U test, while paired samples with non-normal distributions were analyzed using the Wilcoxon signed-rank test. Binary variable comparisons between two groups utilized the Pearson chi-square test. Statistical significance was set at P \u0026lt; .05. Survival curves for 28-day survival trends were generated using the Kaplan-Meier method, and the Fine-Gray test assessed differences in extremity necrosis risk between the groups.\u003c/p\u003e"},{"header":"2. Resuts","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Participants\u003c/h2\u003e \u003cp\u003e Baseline characteristics of the patient groups: From the Department of Critical Care Medicine at the Affiliated Hospital of Hebei University, 85 patients were initially screened. Exclusions included 2 patients who died within 6 hours of admission, 2 with intestinal obstruction, 5 with an ICU stay exceeding 24 hours at enrollment, 1 with glaucoma, and 3 in the acute phase of cerebral hemorrhage. Ultimately, 72 patients were included: 41 in the treatment group and 31 in the control group(Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All patients were on mechanical ventilation; 46 underwent CRRT, and 2 received ECMO. In the treatment group, anisodamine hydrobromide was administered for an average of 3.1 days.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of control and treatment groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTreated (n\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years),\u003c/p\u003e \u003cp\u003eMedian (Q1, Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67(56,75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67(54,76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68(60,71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, male n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18(58%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCraniocerebral injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestinal perforation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(4.17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(7.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(41.67%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(39.02%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(45.16%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholangitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(6.94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(7.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(6.45%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestinal necrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestinal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary tract infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(8.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(7.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(9.68%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastric cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastric perforation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(5.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(7.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine perforation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin and soft tissue infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAppendicitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver abscess\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfective endocarditis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal trauma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestinal tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(4.17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(6.45%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(4.17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(6.45%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntracranial infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeritonsillar inflammation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMain infection site n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35(48.61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(46.34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16(51.61%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiliary system n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(6.94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(7.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(6.45%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal cavity n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(22.22%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(29.27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(12.90%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntracranial n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(4.17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(6.45%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocardium n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestine n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin and soft tissue n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary system n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(8.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(7.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(9.68%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther sites n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(3.23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCondition upon admission to the department\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA(Q1、Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(12,14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(12,14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12(12,15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPEACHii score (Q1, Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(15,16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(15,16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(15,16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote:Both patient groups received septic shock treatment according to the Sepsis-3 Guidelines bundle. The control group additionally received an intravenous infusion of anisodamine hydrobromide alongside standard treatment. Lac denotes blood lactate, ScvO2 central venous oxygen saturation, PcCO2 (v-a) the central venous-arterial carbon dioxide partial pressure difference, PI the pulse perfusion index, SMS the skin mottling score, and CRT the capillary refill time.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Comparison of mortality between treatment and control groups\u003c/h2\u003e \u003cp\u003eThe in-hospital mortality rate for the treatment group was marginally lower than that of the control group, though the difference was not statistically significant (14% vs. 16%; p = .86). The log-rank test of the Kaplan-Meier survival curves indicated no significant survival difference between the groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Comparison of clinical indicators between the treatment group and the control group\u003c/h2\u003e \u003cp\u003eNo significant difference in 28-day mortality was observed between the patient groups. Norepinephrine dosage within 48 hours post-treatment and heart rate at 6 and 4 hours post-treatment showed no significant differences between the groups. However, at 48 hours, the treatment group exhibited a statistically significant decrease in heart rate compared to the control group. ScvO₂ and Pcv-aCO₂ levels showed no significant differences across all time points (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In terms of microcirculatory oxygen metabolism, lactic acid and PI levels significantly improved in the treatment group compared to the control group (P \u0026lt;0.05). SMS scores were lower in the treatment group at 6 and 24 hours post-treatment, with no notable difference at 48 hours. Conversely, CRT scores showed no difference at 6 hours but significantly improved in the treatment group at 24 and 48 hours (P \u0026lt;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)..\u003c/p\u003e \u003cp\u003eRegarding the comparison of oxygen metabolism indicators in the microcirculation between the two groups, levels of lactic acid and perfusion index (PI) were significantly improved in the treatment group compared to the control group (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The Sequential Organ Failure Assessment (SOFA) scores in the treatment group were lower than those in the control group at 6 hours and 24 hours post-treatment, with no significant difference between the groups at 48 hours. Conversely, when comparing the groups using the Capillary Refill Time (CRT) parameter, there was no distinction at 6 hours, but significant improvement was observed in the treatment group at 24 hours and 48 hours (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of primary and secondary clinical outcomes between treatment and control groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTreated (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28-day mortality rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.860\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian NE dosage\u003c/p\u003e \u003cp\u003eMedian(Q1、Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5(0.4,0.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5(0.4,0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5(0.4,0.675)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.880\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.4(0.4,0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4(0.3,0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5(0.4,0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3(0.3,0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3(0.2,0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4(0.3,0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.271\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.1(0.1,0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1(0.1,0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2(0.2,0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.101\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eheart rate\u003c/p\u003e \u003cp\u003emedian(Q1、Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98(84.5,109.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98(78,110)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e99(88,109)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.350\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86.5(75,98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78(68,95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87(78,98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78(67,86.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76(67,86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78(68.5,87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.5(65.75,78.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68(65,76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78(67,89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAC median(Q1、Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.35(2.75,4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2(2.8,4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.4(2.6,3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.945\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1(1.6,3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4(1.3,1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.1(2.1,4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.55(1.375,2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4(1.3,1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5(1.55,4.225)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.35(1.1,2.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1(1,1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.1(1.5,2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eScVO2% median(Q1、Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58(54,65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58(54,65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57(54,65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.750\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64(57.75,65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64(62,65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63(56,65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65(61.75,67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(63,67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64(58,68.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67(63.75,69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67(65,69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68(62,72.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.454\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP(v-a)CO2 median(Q1、Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(6,8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(6,8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(6,8.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.754\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(4,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(5,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(4,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(4,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(4,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(3.5,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.500\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(3,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(4,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(3,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.326\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVariables\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTotal (\u003c/b\u003e\u003cb\u003en\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;72)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eControl (\u003c/b\u003e\u003cb\u003en\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;31)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eTreated (\u003c/b\u003e\u003cb\u003en\u003c/b\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;41)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ep value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI median(Q1、Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.1(0.515,1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1(0.5,1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.1(0.525,0.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.954\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6(1.275,2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7(1.5,2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.28(0.965,1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1(1.4,2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.4(2.1,3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.45(1.07,1.885)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.4(1.875,2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.7(2.4,3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.9(1.8,2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSMS median(Q1、Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(2,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(3,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(3,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.199\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5(1,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(1.5,3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(1,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(0,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRT median(Q1、Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(3,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(3,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(3,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.341\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(3,4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(3,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(3,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.708\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(2,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(2,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(3,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(2,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(2,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(2.5,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Comparison of patients with acral cyanosis progressing to acral necrosis between the two groups.\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003edetails the incidence of acral cyanosis in each group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAcrocyanosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo acral cyanosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStatistic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9(21.95%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32(78.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eχ\u0026sup2;=1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10(32.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21(67.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003edf\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19(26.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e53(73.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of acral cyanosis events progressing to necrosis and mortality across two patient groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLimb Necrosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDeath (Competing event)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCensored\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFine-Gray competing risks analysis results.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003esHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment vs Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u0026ndash;3.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003esHR: Subdistribution Hazard Ratio\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSymmetric peripheral gangrene (SPG) is characterized by cyanosis and ecchymosis of the extremities, typically starting at the fingers and progressing proximally, potentially leading to necrosis, ulcers, and ultimately gangrene. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e compares acrocyanosis occurrence between two patient groups. In the experimental group, 9 out of 41 cases (21.95%) exhibited acrocyanosis, whereas in the control group, 10 out of 31 cases (32.26%) showed this symptom. A chi-square test yielded X2\u0026thinsp;=\u0026thinsp;1.12, df\u0026thinsp;=\u0026thinsp;1, and P = .29, indicating no statistically significant difference in acrocyanosis incidence between the groups. Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e details patient outcomes with acral cyanosis. In the control group, 2 out of 10 patients (20%) progressed to acral necrosis, 4 (40.%) died before necrosis could be observed, and 4 (40.%) did not develop necrosis. In the experimental group, 1 out of 9 patients (11.1%) progressed to acral necrosis, 4 (44.4%) died before necrosis observation, and 4 (44.4%) did not develop necrosis. The Fine-Gray competing risk model (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) yielded a sub-distribution hazard ratio (sHR) of .51 (95% CI: .07\u0026ndash;3.48) for the experimental group compared to the control, with a P-value of 0.49, indicating no significant difference in acral necrosis risk between the groups.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eAdvancements in septic shock treatments reveal that achieving macro-hemodynamic stability is merely a component of sepsis management; the primary objective is optimizing microvascular blood flow. Septic shock often disrupts \"hemodynamic coherence,\" indicating a disconnect between systemic and microcirculatory responses\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Clinically, using high-dose vasoactive drugs to maintain mean arterial pressure (MAP) above 65 mmHg frequently results in extremity necrosis\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Effective organ and tissue perfusion necessitates optimizing microcirculatory regulation\u0026mdash;targeting arterioles, capillaries, and venules\u0026mdash;rather than solely maintaining blood pressure, which can lead to peripheral vascular occlusion\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Thus, identifying methods and drugs to enhance microcirculation is imperative.\u003c/p\u003e \u003cp\u003eThis study assessed anisodamine hydrobromide's impact on microcirculation and clinical outcomes. No significant difference in 28-day mortality was observed between the groups, likely due to the multifactorial nature of septic shock, which involves complex interactions such as multiple organ failure, gastrointestinal ischemia, and the adequacy of cardiopulmonary resuscitation \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. While anisodamine hydrobromide enhances microcirculation, it may not mitigate other lethal risk factors like uncontrolled infection sources and organ failure. The \"macrovasodilation and microvasoconstriction\" seen in septic shock reflects pathological disparities in systemic inflammatory responses and vascular regulation across different vessel levels, influenced by vascular structure, regulatory mechanisms, and local microenvironment changes \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. The tension in large blood vessels, such as the aorta, middle artery, and vein, is primarily influenced by neurohumoral regulation and systemic inflammatory mediators\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Infections activate immune cells to release inflammatory factors like TNF-α and IL-6, prompting cells in the liver, kidney, and intestine to produce substantial amounts of nitric oxide (NO)\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. As a potent vasodilator, NO penetrates vascular smooth muscle cells, activating guanylate cyclase and increasing cGMP, which leads to smooth muscle relaxation. Research indicates that anisodamine hydrobromide's antishock effect is mediated by IL-10, and this effect is significantly reduced in IL-10-deficient mice\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. However, not all septic shock patients exhibit elevated IL-10 levels; insufficient anti-inflammatory compensation can result in an excessive pro-inflammatory response, causing severe tissue damage. This impairs immune cell function, diminishes pathogen clearance, complicates infection control, and worsens prognosis. In such cases, the antishock efficacy of anisodamine hydrobromide is limited. The lack of statistical difference in norepinephrine (NE) dosage between the two groups within 48 hours post-treatment can be attributed to the regulation of large vessel tension primarily by sympathetic nerves (via α-adrenergic receptors), the renin-angiotensin system, and humoral factors like catecholamines and endothelin\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. M-choline receptors are sparsely distributed on smooth muscle cells. Anisodamine hydrobromide, a selective M-choline receptor antagonist, primarily affects M-receptors on small vessel smooth muscle, alleviating spasms by counteracting acetylcholine and other vasoconstrictors. In contrast, its direct impact on large vessels such as the aorta, superior mesenteric artery, and renal artery is minimal due to the low density of M receptors, thus not significantly altering basal tension. Consequently, any improvement in blood pressure or reduction in blood pressure medication is negligible.\u003c/p\u003e \u003cp\u003eMacrocirculatory parameters, such as central venous oxygen saturation (ScvO₂) and the central veno-arterial carbon dioxide gradient (Pcv-aCO₂), are often used to evaluate systemic oxygen metabolism and tissue perfusion \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. In this study, no significant differences in ScvO₂ and Pcv-aCO₂ were observed between the treatment and control groups at any time point. This suggests that anisodamine hydrobromide primarily enhances microcirculation perfusion with minimal impact on systemic oxygen metabolism. Whole-body oxygen metabolism is influenced by factors such as respiratory function and hemoglobin levels. Following microcirculation improvement by anisodamine hydrobromide, noticeable changes in systemic oxygen metabolism may require extended time or complex physiological adjustments.\u003c/p\u003e \u003cp\u003eIn the microcirculation oxygen metabolism index, the lactic acid levels in the PI treatment group showed a significant improvement compared to the control group. Lactate is crucial for diagnosing and assessing septic shock \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e and serves as a vital marker of tissue hypoxia and anaerobic metabolism \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. A reduction in lactate levels suggests that anisodamine hydrobromide effectively alleviates tissue hypoxia. This effect is attributed to anisodamine hydrobromide's ability to block M choline receptors on vascular smooth muscle, thereby alleviating microvasospasm (including arterioles, venules, and pre-capillary sphincters), stabilizing the endothelium, and inhibiting microthrombosis \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Enhancing microcirculatory blood flow improves tissue and organ oxygenation. Correcting tissue hypoxia mitigates anaerobic metabolism, thereby lowering lactic acid production and blood lactate levels. The perfusion index (PI), indicating local tissue blood flow, is calculated as the ratio of the pulse wave in pulsating to non-pulsating regions. While research on macrocirculatory stability in septic shock patients is well-established, microcirculation has emerged as a focal point of study. It is recognized that microcirculatory failure is a fundamental pathological feature of septic shock, with clinical challenges often arising from the decoupling of macro- and microcirculation \u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. During septic shock, the release of inflammatory mediators like TNF-α and IL-6, along with sympathetic excitation and vasoactive substances such as catecholamines and angiotensin, induces persistent spasms and contractions in systemic microvessels, particularly arterioles and precapillary sphincters. This phenomenon effectively \"blocks\" the microcirculation pathway entrance, hindering blood flow into the capillary bed and leading to tissue ischemia and hypoxia\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. The study's observed improvement in PI underscores the regulatory impact of anisodamine hydrobromide on microcirculation, enhancing microvascular perfusion and tissue oxygenation. These findings indicate that anisodamine hydrobromide significantly improves microcirculatory oxygen metabolism, playing a crucial role in alleviating tissue hypoxia in septic shock patients.\u003c/p\u003e \u003cp\u003eThe speckle score (SMS) was employed as a specific index to assess peripheral microcirculation disorders in shock severity\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Scores for the treatment group were significantly lower than those of the control group at 6 and 24 hours post-treatment, with no significant difference observed at 48 hours. The speckle score quantifies the extent and duration of skin speckle, directly reflecting the perfusion state of skin microcirculation. The early-stage decrease in scores suggests that anisodamine hydrobromide rapidly restores microcirculation perfusion in peripheral tissues, such as skin, by alleviating arteriolar spasm and improving capillary blood flow. However, the score difference diminished at 48 hours, possibly due to improved microcirculation in the control group from overall treatment measures like fluid resuscitation and antibiotic intervention. Additionally, the speckle score's sensitivity may decline in the later shock stages, as vascular endothelial damage from prolonged hypoxia necessitates more complex repair mechanisms\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDistal gangrene in septic shock patients typically signals severe hypotension or elevated vasoconstrictor drug use, manifesting symmetrically or locally in fingers, toes, and potentially extending to feet or legs\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. Unlike large artery occlusion, SPG arises from microvascular dysfunction and small vessel thrombosis\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. This pathophysiology likely stems from a significant imbalance between procoagulant and anticoagulant factors within the tissue vascular bed, leading to microthrombosis\u003csup\u003e[32、33]\u003c/sup\u003e. Anisodamine hydrobromide theoretically inhibits microthrombosis, yet the study failed to confirm its efficacy in reversing acrocyanosis and necrosis. This may be due to acrocyanosis necrosis being the end-stage manifestation of microcirculation disorders, which involves not only microthrombosis but also factors like vascular endothelial injury, apoptosis, and metabolic failure from prolonged tissue ischemia. Anisodamine hydrobromide primarily acts by inhibiting thromboxane synthesis and improving early microcirculation blood flow. However, it is insufficient as a single intervention to halt necrosis driven by irreversible cellular damage and multifactorial tissue necrosis. Its impact on microcirculation is more apparent in hemodynamic measures, such as improved perfusion index (PI) and reduced lactate (LAC) levels. Nonetheless, acronecrosis results from long-term severe ischemia, and short-term hemodynamic improvements may not fully reverse ischemic tissue damage, thus inadequately reducing necrosis incidence. Additionally, the study's small sample size warrants consideration, suggesting the need for larger-scale research to delve deeper into this area.\u003c/p\u003e \u003cp\u003eAnisodamine hydrobromide effectively enhances early microcirculation oxygen metabolism, reduces heart rate, and improves peripheral circulation in septic shock patients. While it did not significantly impact 28-day mortality, NE dosage, systemic oxygen metabolism, or limb necrosis improvement in this study, its efficacy in addressing microcirculation disorders remains notable. Future research should increase sample size, extend observation periods, and investigate the mechanisms and combined effects with other treatments to develop more effective strategies for septic shock management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e This study was reviewed and approved by the Ethics Committee of The Affiliated Hospital of Hebei University (Approval No. HDFY-KY-2024-001). Informed consent was obtained from all individual participants included in the study. This study is not a clinical trial. Clinical trial number: not applicable.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eAll participants provided informed consent for the publication of their anonymized data. Written informed consent for publication was obtained for this manuscript for any case details, images, or other potentially identifiable information.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by the Baoding Science and Technology Bureau under Grant 2241ZF098.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eXiaoxu Ding and Liwei Yan contributed equally to this work. X.D. and L.Y.: Conceptualization, Methodology, Investigation, Writing \u0026ndash; Original Draft. Q.Y. and X.Z.: Formal analysis, Visualization, Writing \u0026ndash; Review \u0026amp; Editing. Z.Y. and H.L.: Supervision, Funding acquisition, Project administration. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Due to privacy and ethical concerns, supporting data cannot be made openly available. Access requests will be assessed on a case-by-case basis in compliance with the approved ethical protocol.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDe Backer D, Ricottilli F, Ospina-Tasc\u0026oacute;n GA. Septic shock: a microcirculation disease. Curr Opin Anaesthesiol. 2021;34(2):85\u0026ndash;91. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ACO.0000000000000957\u003c/span\u003e\u003cspan address=\"10.1097/ACO.0000000000000957\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDamiani E, Carsetti A, Casarotta E, Domizi R, Scorcella C, Donati A, Adrario E. Microcirculation-guided resuscitation in sepsis: the next frontier? 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PMID: 33627309.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Anisodamine hydrobromide, Septic shock, Microcirculation disorder, Blood lactic acid (LAC), Peripheral perfusion index (PI), Mottling score, Acral cyanosis, Acral necrosis","lastPublishedDoi":"10.21203/rs.3.rs-8704388/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8704388/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e \u003cp\u003eSeptic shock, prevalent in critical care medicine, poses significant treatment challenges and high mortality rates. Its pathogenesis involves an inflammatory cytokine storm and microcirculatory dysfunction, potentially leading to fatal multiple organ failure. Microcirculation alterations during septic shock critically impact patient outcomes. Anisodamine hydrobromide, a commonly used anticholinergic, mitigates oxidative stress and modulates cell apoptosis, notably enhancing microcirculation by targeting cholinergic receptors. This study investigates the efficacy of anisodamine hydrobromide in ameliorating microcirculatory disorders in septic shock patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e This article collects 72 cases of patients with septic shock from the Department of Critical Care Medicine, Affiliated Hospital of Hebei University from 2020 to 2024. Participants were assigned to either a treatment group or a control group based on the administration of anisodamine hydrobromide. Data on heart rate, mean arterial pressure (MAP), blood lactate (LAC) levels, peripheral blood perfusion index (PI), and mottling scores were collected at 0, 6, 24, and 48 hours post-admission. Additionally, the 28-day mortality rate and progression from acral cyanosis to acral necrosis were assessed. Statistical analysis was conducted to compare differences in these indices between the groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eNo statistically significant difference was observed in 28-day mortality between the treatment and control groups (14% vs. 16%; p\u0026thinsp;=\u0026thinsp;0.86). Norepinephrine dosage also showed no significant difference. Heart rates at 6 and 24 hours post-treatment were statistically similar; however, at 48 hours, the treatment group exhibited a significantly lower heart rate than the control group. ScvO2 and Pcv-aCO2 levels did not differ significantly between groups at any time point (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Comparison of microcirculatory oxygen metabolism indicators between the groups: The treatment group exhibited significant improvements in lactate and PI compared to the control group (P \u0026lt;0.05). At 6 and 24 hours post-treatment, the SMS scores were lower in the treatment group, though no significant difference was observed at 48 hours. CRT showed no difference at 6 hours, but the treatment group demonstrated significant improvement at 24 and 48 hours (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). No statistically significant difference was found in the progression from acral cyanosis to acral necrosis between the groups.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe standardized treatment of septic shock, when combined with anisodamine hydrobromide infusion, enhances early microcirculation indicators in septic shock patients.\u003c/p\u003e","manuscriptTitle":"Effect of anisodamine hydrobromide on improving early microcirculation disturbance in septic shock patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-23 17:32:52","doi":"10.21203/rs.3.rs-8704388/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8c187831-e2c6-4d57-a232-b10d0c20191d","owner":[],"postedDate":"February 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-09T06:56:38+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-23 17:32:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8704388","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8704388","identity":"rs-8704388","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}