Early peripheral perfusion index predicts 28-day outcome in patients with septic shock

BACKGROUND:To investigate the prognostic value of the peripheral perfusion index(PPI)in patients with septic shock.METHODS:This prospective cohort study,conducted at the emergency intensive care unit of Peking University People's Hospital,recruited 200 patients with septic shock between January 2023 and August 2023.These patients were divided into survival(n=84)and death(n=116)groups based on 28-day outcomes.Clinical evaluations included laboratory tests and clinical scores,with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission.Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses.Receiver operator characteristic(ROC)curve was used to assess predictive performance.Mortality rates were compared,and Kaplan-Meier survival plots were created.RESULTS:Compared to the survival group,patients in the death group were older and had more severe liver damage and coagulation dysfunction,necessitating higher norepinephrine doses and increased fl uid replacement.Higher lactate levels and lower PPI levels at 0 h,6 h,and 12 h were observed in the death group.Multivariate Cox regression identifi ed prolonged prothrombin time(PT),decreased 6-h PPI and 12-h PPI as independent risk factors for death.The area under the curves for 6-h PPI and 12-h PPI were 0.802(95%CI 0.742-0.863,P<0.001)and 0.945(95%CI 0.915-0.974,P<0.001),respectively,which were superior to Glasgow Coma Scale(GCS),Sequential Organ Failure Assessment(SOFA)scores(0.864 and 0.928).Cumulative mortality in the low PPI groups at 6 h and 12 h was signifi cantly higher than in the high PPI groups(6-h PPI:77.52%vs.22.54%;12-h PPI:92.04%vs.13.79%,P<0.001).CONCLUSION:PPI may have value in predicting 28-day mortality in patients with septic shock.

Knowledge,management,and complications of sepsis and septic shock:A significant therapeutic challenge in the intensive care unit

Sepsis and septic shock are life-threatening conditions that are globally responsible for almost 20%of mortality,especially in low and middle-income countries.This review was conducted on PubMed and Google Scholar databases with keywords sepsis,septic shock,sepsis management,and sepsis complications.Articles published up to July 2023 in English were included.Diagnosis and management should be carried out without unnecessary delay.Cooperation between various medical specialties including intensive care doctors,neurologists,hepatologists,cardiologists,and pediatric doctors is needed if a child is affected.New strategies have to be implemented in low and middle-income countries to decrease the sepsis incidence and reduce mortality in the population.

Systematic review with expert consensus on use of extracorporeal hemoadsorption in septic shock:An Indian perspective

BACKGROUND Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters.Despite standard therapy,the outcomes are poor.Newer adjuvant therapy,such as CytoSorb®extracorporeal haemoadsorption device,has been investigated and shown promising outcome.However,there is a lack of some guidance to make clinical decisions on the use of CytoSorb®haemoadsorption as an adjuvant therapy in septic shock in Indian Setting.Therefore,this expert consensus was formulated.AIM To formulate/establish specific consensus statements on the use of CytoSorb®haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario.METHODS We performed a comprehensive literature on CytoSorb®haemoadsorption in sepsis,septic shock in PubMed selecting papers published between January 2011 and March 20232021 in English language.The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps.Using a modified Delphi approach combining evidence appraisal and expert opinion,the following topics related to CytoSorb®in septic shock were addressed:need for adjuvant therapy,initiation timeline,need for Interleukin-6 levels,duration of therapy,change of adsorbers,safety,prerequisite condition,efficacy endpoints and management flowchart.Eleven expert members from critical care,emergency medicine,and the intensive care participated and voted on nine statements and one open-ended question.RESULTS Eleven expert members from critical care,emergency medicine,and the intensive care participated and voted on nine statements and one open-ended question.All 11 experts in the consensus group(100%)participated in the first,second and third round of voting.After three iterative voting rounds and adapting two statements,consensus was achieved on nine statements out of nine statements.The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb®for all indications in the open-ended question(Q10)focusing on“future recommendations for CytoSorb®therapy”.CONCLUSION This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb®haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.

Low T3 vs low T3T4 euthyroid sick syndrome in septic shock patients:A prospective observational cohort study

BACKGROUND Both phases of euthyroid sick syndrome(ESS)are associated with worse prognosis in septic shock patients.Although there are still no indications for supplementation therapy,there is no evidence that both phases(initial and prolonged)are adaptive or that only prolonged is maladaptive and requires supplementation.AIM To analyze clinical,hemodynamic and laboratory differences in two groups of septic shock patients with ESS.METHODS A total of 47 septic shock patients with ESS were divided according to values of their thyroid hormones into low T3 and low T3T4 groups.The analysis included demographic data,mortality scores,intensive care unit stay,mechanical ventilation length and 28-day survival and laboratory with hemodynamics.RESULTS The Simplified Acute Physiology Score II score(P=0.029),dobutamine(P=0.003)and epinephrine requirement(P=0.000)and the incidence of renal failure and multiple organ failure(MOF)(P=0.000)were significantly higher for the low T3T4.Hypoalbuminemia(P=0.047),neutrophilia(P=0.038),lymphopenia(P=0.013)and lactatemia(P=0.013)were more pronounced on T2 for the low T3T4 group compared to the low T3 group.Diastolic blood pressure at T0(P=0.017)and T1(P=0.007),as well as mean arterial pressure at T0(P=0.037)and T2(P=0.033)was higher for the low T3 group.CONCLUSION The low T3T4 population is associated with higher frequency of renal insufficiency and MOF,with worse laboratory and hemodynamic parameters.These findings suggest potentially maladaptive changes in the chronic phase of septic shock.

Efficacy and safety of ulinastatin in the treatment of septic shock:a systematic review and meta-analysis

Background:Septic shock is a common systemic inflammatory response syndrome for critical patients in the intensive care unit.Ulinastatin is currently used for the treatment of septic shock.Our study sought to evaluate the efficacy and safety of ulinastatin in the treatment of septic shock patients.Methods:Three English databases(Embase,Medline,and Cochrane Library)and four Chinese databases(China National Knowledge Infrastructure,Wanfang data,SinoMed,and VIP)were searched for published randomized controlled trials.Stata 16.0 software was used to conduct the meta-analysis.Results:A total of 48 articles were included(Chinese article 47,1 in English).The results show that the treatment of ulinastatin could reduce mortality(risk ratio=0.63,95%confidence interval(CI)(0.55,0.72)),multiple organ dysfunction syndrome(risk ratio=0.6,95%CI(0.53,0.68)),length of intensive care unit stay(mean difference(MD)=-3.92,95%CI(-4.65,-3.18)),length of hospital stay(MD=-4.39,95%CI(-6.63,-2.15))and decrease Acute Physiology and Chronic Health Evaluation II score(MD=-4.55,95%CI(-5.63,-3.47))and Sequential Organ Failure Assessment score(MD=-2.02,95%CI(-2.59,-1.44))with P<0.001.Moreover,it lowers TNF-α(standardized mean difference(SMD)=-1.78,95%CI(-2.24,-1.32)),Interleukin-6(SMD=-1.17,95%CI(-1.55,-0.8)),C reactive protein(SMD=-1.49,95%CI(-1.99,-0.99)),hypersensitive C-reactive protein(SMD=-1.9,95%CI(-2.87,-0.94))and procalcitonin(SMD=-0.89,95%CI(-1.12,-0.67))levels in the body.Conclusions:Available evidence shows that ulinastatin reduces case mortality rate,multiple organ dysfunction syndrome,length of intensive care unit stay,and length of hospital stay and decreases Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score.Moreover,it also lowers TNF-α,Interleukin-6,C reactive protein,hypersensitive C-reactive protein,and procalcitonin levels in the body.

Hypoperfusion context as a predictor of 28-d all-cause mortality in septic shock patients:A comparative observational study

BACKGROUND As per the latest Surviving Sepsis Campaign guidelines,fluid resuscitation should be guided by repeated measurements of blood lactate levels until normalization.Nevertheless,raised lactate levels should be interpreted in the clinical context,as there may be other causes of elevated lactate levels.Thus,it may not be the best tool for real-time assessment of the effect of hemodynamic resuscitation,and exploring alternative resuscitation targets should be an essential research priority in sepsis.AIM To compare the 28-d mortality in two clinical patterns of septic shock:hyperlactatemic patients with hypoperfusion context and hyperlactatemic patients without hypoperfusion context.METHODS This prospective comparative observational study carried out on 135 adult patients with septic shock that met Sepsis-3 definitions compared patients with hyperlactatemia in a hypoperfusion context(Group 1,n=95)and patients with hyperlactatemia in a non-hypoperfusion context(Group 2,n=40).Hypoperfusion context was defined by a central venous saturation less than 70%,central venousarterial PCO_(2)gradient[P(cv-a)CO_(2)]≥6 mmHg,and capillary refilling time(CRT)≥4 s.The patients were observed for various macro and micro hemodynamic parameters at regular intervals of 0 h,3 h,and 6 h.All-cause 28-d mortality and all other secondary objective parameters were observed at specified intervals.Nominal categorical data were compared using theχ^(2)or Fisher’s exact test.Nonnormally distributed continuous variables were compared using the Mann-Whitney U test.Receiver operating characteristic curve analysis with the Youden index determined the cutoff values of lactate,CRT,and metabolic perfusion parameters to predict the 28-d all-cause mortality.A P value of<0.05 was considered significant.RESULTS Patient demographics,comorbidities,baseline laboratory,vital parameters,source of infection,baseline lactate levels,and lactate clearance at 3 h and 6 h,Sequential Organ Failure scores,need for invasive mechanical ventilation,days on mechanical ventilation,and renal replacement therapy-free days within 28 d,duration of intensive care unit stay,and hospital stay were comparable between the two groups.The stratification of patients into hypoperfusion and nonhypoperfusion context did not result in a significantly different 28-d mortality(24%vs 15%,respectively;P=0.234).However,the patients within the hypoperfusion context with high P(cva)CO_(2)and CRT(P=0.022)at baseline had significantly higher mortality than Group 2.The norepinephrine dose was higher in Group 1 but did not achieve statistical significance with a P>0.05 at all measured intervals.Group 1 had a higher proportion of patients requiring vasopressin and the mean vasopressor-free days out of the total 28 d were lower in patients with hypoperfusion(18.88±9.04 vs 21.08±8.76;P=0.011).The mean lactate levels and lactate clearance at 3 h and 6 h,CRT,P(cv-a)CO_(2)at 0 h,3 h,and 6 h were found to be associated with 28-d mortality in patients with septic shock,with lactate levels at 6 h having the best predictive value(area under the curve lactate at 6 h:0.845).CONCLUSION Septic shock patients fulfilling the hypoperfusion and non-hypoperfusion context exhibited similar 28-d all-cause hospital mortality,although patients with hypoperfusion displayed a more severe circulatory dysfunction.Lactate levels at 6 h had a better predictive value in predicting 28-d mortality than other parameters.Persistently high P(cv-a)CO_(2)(>6 mmHg)or increased CRT(>4 s)at 3 h and 6 h during early resuscitation can be a valuable additional aid for prognostication of septic shock patients.

Emerging concepts in the care of patients with cirrhosis and septic shock

Septic shock impacts approximately 6% of hospitalized patients with cirrhosis and is associated with high rates of morbidity and mortality. Although a number of landmark clinical trials have paved the way for incremental improvements in the diagnosis and management of septic shock in the general population, patients with cirrhosis have largely been excluded from these studies and critical knowledge gaps continue to impact the care of these individuals. In this review,we discuss nuances in the care of patients with cirrhosis and septic shock using a pathophysiology-based approach. We illustrate that septic shock may be challenging to diagnose in this population in the context of factors such as chronic hypotension, impaired lactate metabolism, and concomitant hepatic encephalopathy. Furthermore, we demonstrate that the application of routine interventions such as intravenous fluids, vasopressors, antibiotics, and steroids should be carefully considered among those with decompensated cirrhosis in light of hemodynamic, metabolic, hormonal, and immunologic disturbances. We propose that future research should include and characterize patients with cirrhosis in a systematic manner, and clinical practice guidelines may need to be refined accordingly.

Continuous renal replacement therapy with oXiris®in patients with hematologically malignant septic shock:A retrospective study

BACKGROUND The mortality rate from septic shock in patients with hematological malignancies(HMs)remains significantly higher than that in patients without HMs.A longer resuscitation time would definitely be harmful because of the irreversibly immunocompromised status of the patients.Shortening the resuscitation time through continuous renal replacement therapy(CRRT)with oXiris^(■)would be an attractive strategy in managing such patients.AIM To explore the effects of CRRT and oXiris^(■)in shortening the resuscitation time and modifying the host response by reducing inflammation mediator levels.METHODS Forty-five patients with HM were diagnosed with septic shock and underwent CRRT between 2018 and 2022.Patients were divided into two groups based on the hemofilter used for CRRT(oXiris^(■)group,n=26;M150 group,n=19).We compared the number of days of negative and total fluid balance after 7 d of CRRT between the groups.The heart rate,norepinephrine dose,Sequential Organ Failure Assessment(SOFA)score,and blood lactic acid levels at different time points in the two groups were also compared.Blood levels of inflammatory mediators in the 26 patients in the oXiris^(■)group were measured to further infer the possible mechanism.RESULTS The average total fluid balance after 7 d of CRRT in the oXiris^(■)group was significantly lower than that of patients in the M150 hemofilter group.The SOFA scores of patients after CRRT with oXiris^(■)therapy were significantly lower than those before treatment on day 1(d1),d3 and d7 after CRRT;these parameters were also significantly lower than those of the control group on d7.The lac level after oXiris^(■)therapy was significantly lower than that before treatment on d3 and d7 after CRRT.There were no significant differences in the above parameters between the two groups at the other time points.In the oXiris^(■)group,procalcitonin levels decreased on d7,whereas interleukin-6 and tumor necrosis factor levels decreased significantly on d3 and d7 after treatment.CONCLUSION CRRT with oXiris^(■)hemofilter may improve hemodynamics by reducing inflammatory mediators and playing a role in shortening the resuscitation period and decreasing total fluid balance in the resuscitation phases.

Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review

Septic shock treatment remains a major challenge for intensive care units,despite the recent prominent advances in both management and outcomes.Vasopressors serve as a cornerstone of septic shock therapy,but there is still controversy over the timing of administration.Specifically,it remains unclear whether vasopressors should be used early in the course of treatment.Here,we provide a systematic review of the literature on the timing of vasopressor administration.Research was systematically identified through PubMed,Embase and Cochrane searching according to PRISMA guidelines.Fourteen studies met the eligibility criteria and were included in the review.The pathophysiological basis for early vasopressor use was classified,with the exploration on indications for the early administration of mono-vasopressors or their combination with vasopressin or angiotensinII.We found that mortality was 28.1%-47.7%in the early vasopressors group,and 33.6%-54.5%in the control group.We also investigated the issue of vasopressor responsiveness.Furthermore,we acknowledged the subsequent challenge of administration of high-dose norepinephrine via peripheral veins with early vasopressor use.Based on the literature review,we propose a possible protocol for the early initiation of vasopressors in septic shock resuscitation.

Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats

BACKGROUND: Dexmedetomidine has already been used in septic patients as a new sedative agent, few studies have examined its effects on immunomodulation. Therefore, the authors have designed a controlled experimental study to characterize the immunomodulation effects of dexmedetomidine in the cecal ligation and puncture(CLP) model in rats. METHODS: After CLP, 48 Wistar rats were randomly allocated into four groups:(1) CLP group;(2) small-dose treatment group(2.5 g·kg^(-1)·h^(-1));(3) medium-dose treatment group(5.0 g·kg^(-1)·h^(-1)); and(4) large-dose treatment group(10.0 g·kg^(-1)·h^(-1)). HLA-DR and plasma cytokine(IL-4, IL-6, IL-10 and TNF-α) levels were measured, and the mean arterial blood pressure(MAP), heart rate(HR), arterial blood gases, lactate concentrations and mortality were also documented. RESULTS: The HLA-DR level, inflammatory mediator levels, MAP and HR had no obvious changes among Dexmedetomidine treatment groups(DEX groups). Compared with the CLP group, the DEX groups exhibited decreased HLA-DR levels(P_(group)=0.0202) and increased IL-6 production, which was increased at 3 h(P= 0.0113) and was then attenuated at 5 h; additionally, the DEX groups exhibited decreased HR(P<0.001) while maintaining MAP(P_(group)=0.1238), and remarkably improving lactate(P<0.0001). All of these factors led to a significant decrease in the mortality, with observed rates of 91.7%, 66.7%, 25% and 18% for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively.CONCLUSION: Dexmedetomidine treatment in the setting of a CLP sepsis rat model has partially induced immunomodulation that was initiated within 5 h, causing a decreased HR while maintaining MAP, remarkably improving metabolic acidosis and improving mortality dosedependently.

Association of polymorphisms of IL and CD14 genes with acute severe pancreatitis and septic shock

AIM. To investigate IL-1β＋3 594 in the 5^th intron, IL-10-1 082 and CD14-159 polymorphisms in patients with acute pancreatitis （AP） and septic shock.METHODS： The study induded 215 patients （109 with acute severe pancreatitis （SAP）, 106 with acute mild pancreatitis （MAP）） and 116 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of PCR products.RESULTS： The frequencies of IL-β＋3 594T, IL-10-1082G and CD14-159T allele were similar in patients with mild or severe pancreatitis and in controls. Within SAP patients, no significant differences were found in the allele distribution examined when etiology was studied again. Patients with septic shock showed a significantly higher prevalence of IL-10-1082G allele than those without shock （X^2 = 5.921,P= 0.015）.CONCLUSION： IL-10-1082G plays an important role in the susceptibility of SAP patients to septic shock. Genetic factors are not important in determination of disease severity or susceptibility to AP.

Speckle-tracking echocardiography for detecting myocardial dysfunction in sepsis and septic shock patients:A single emergency department study

BACKGROUND:Septic cardiomyopathy(SCM)occurs in the early stage of sepsis and septic shock,which has implications for treatment strategies and prognosis.Additionally,myocardial involvement in the early stages of sepsis is difficult to identify.Here,we assess subclinical myocardial function using laboratory tests and speckle-tracking echocardiography(STE).METHODS:Emergency department patients diagnosed with sepsis or septic shock were included for analysis.Those with other causes of acute or pre-existing cardiac dysfunction were excluded.Transthoracic echocardiography(TTE),including conventional echocardiography and STE,were performed for all patients three hours after initial resuscitation.Samples for laboratory tests were taken around the time of TTE.RESULTS:Left ventricular functions of 60 patients were analyzed,including 21 septic shock patients and 39 sepsis patients.There was no significant difference in global longitudinal strain(GLS),global circumferential strain(GCS),or global radical strain(GRS)between patients with sepsis and septic shock(all with P>0.05).However,GLS and GCS were significantly less negative in patients with abnormal troponin levels or in patients with abnormal left ventricular ejection fraction(LVEF)values(all with P<0.05).There were also moderate correlations between GLS and levels of cTnI(r=0.40,P=0.002)or N-terminal pro-B-type natriuretic peptide(NT-proBNP)(r=0.44,P=0.001)in sepsis and septic shock patients.CONCLUSION:Myocardial dysfunction,e.g.,lower LVEF or less negative GLS in patients with sepsis or septic shock,is more affected by myocardial injury.GLS could be incorporated into mainstream clinical practice as a supplementary LVEF parameter,especially for those with elevated troponin levels.

Effect of early goal directed therapy on tissue perfusion in patients with septic shock

BACKGROUND:This study aimed to observe the effect of early goal directed therapy(EGDT)on tissue perfusion,microcirculation and tissue oxygenation in patients with septic shock.METHODS:Patients with early septic shock(<24 hours) who had been admitted to the ICU of Zhongda Hospital Affiliated to Southeast University from September 2009 through May 2011 were enrolled(research time:12 months),and they didn't meet the criteria of EGDT.Patients who had one of the following were excluded:stroke,brain injury,other types of shock,severe heart failure,acute myocardial infarction,age below 18 years,pregnancy,end-stage disease,cardiac arrest,extensive burns,oral bleeding,difficulty in opening the mouth,and the onset of septic shock beyond 24 hours.Patients treated with the standard protocol of EGDT were included.Transcutaneous pressure of oxygen and carbon dioxide(PtcO_2,PtcCO_2) were monitored and hemodynamic measurements were obtained.Side-stream dark field(SDF) imaging device was applied to obtain sublingual microcirculation.Hemodynamics,tissue oxygen,and sublingual microcirculation were compared before and after EGDT.If the variable meets the normal distribution,Student's t test was applied.Otherwise,Wilcoxon's rank-sum test was used.Correlation between variables was analyzed with Pearson's product-moment correlation coefficient method.RESULTS:Twenty patients were involved,but one patient wasn't analyzed because he didn't meet the EGDT criteria.PtcO_2 and PtcCO_2 were monitored in 19 patients,of whom sublingual microcirculation was obtained.After EGDT,PtcO_2 increased from 62.7+24.0 mmHg to 78.0±30.9mmHg(P<0.05) and tissue oxygenation index(PtcO_2/FiO_2) was 110.7+60.4 mmHg before EGDT and 141.6±78.2 mmHg after EGDT(P<0.05).The difference between PtcCO_2 and PCO_2 decreased significantly after EGDT(P<0.05).The density of perfused small vessels(PPV) and microcirculatory flow index of small vessels(MFI) tended to increase,but there were no significant differences between them(P>0.05).PtcO_2,PtcO_2/FiO_2,and PtcCO_2 were not linearly related to central venous saturation,lactate,oxygen delivery,and oxygen consumption(P>0.05).CONCLUSION:Peripheral perfusion was improved after EGDT in patients with septic shock,and it was not exactly reflected by the index of systemic perfusion.

Efficacy and safety of corticosteroids in immunocompetent patients with septic shock

BACKGROUND: The use of corticosteroids in septic shock has been studied for many decades but yielded conflicting results. We conducted a systematic review to evaluate the efficacy and the safety of corticosteroids in immunocompetent patients with septic shock.METHODS: Medline via Pub Med, Cochrane Central Register of Controlled Trials(CENTRAL) in the Cochrane Library, and EMBASE were searched from inception to March 2020. Two reviewers independently identified randomized controlled trials(RCTs) comparing corticosteroids with a control group for immunocompetent patients with septic shock. Data were abstracted and reported following the Cochrane Handbook for Systematic Review of Intervention and Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) statement. The efficacy outcome included mortality and shock reversal. The safety outcomes were infection, gastrointestinal bleeding, and hyperglycemia.RESULTS: Nine RCTs with a total of 1,298 patients were included. Compared with the control group, corticosteroid group did not lower the short-term(28 or 30 days) mortality(risk ratio [RR] 0.95, 95% confidence interval(CI) 0.85 to 1.06, inconsistency [I2]=0%, trial sequential analysis [TSA]-adjusted CI 0.83 to 1.09, moderate-certainty evidence). Corticosteroids significantly shortened the time to shock reversal compared with the control group(mean difference [MD] –21.56 hours;95% CI –32.95 to –10.16, I2=0%;TSA-adjusted CI –33.33 to –9.78, moderate-certainty evidence). The corticosteroid treatment was associated with an increased risk of hyperglycemia but not the infection or gastrointestinal bleeding.CONCLUSIONS: The corticosteroid treatment is not associated with lower short-or longterm mortality compared with placebo in immunocompetent patients with septic shock. However, corticosteroids significantly shorten the time to shock reversal without increasing the risk of infection. The patient's immune status should also be considered during clinical treatment and clinical trials in future.

Association of fluid balance trajectories with clinical outcomes in patients with septic shock:A prospective multicenter cohort study

Background:Septic shock has a high incidence and mortality rate in Intensive Care Units(ICUs).Earlier intravenous fluid resuscitation can significantly improve outcomes in septic patients but easily leads to fluid overload(FO),which is associated with poor clinical outcomes.A single point value of fluid cannot provide enough fluid information.The aim of this study was to investigate the impact of fluid balance(FB)latent trajectories on clinical outcomes in septic patients.Methods:Patients were diagnosed with septic shock during the first 48 h,and sequential fluid data for the first 3 days of ICU admission were included.A group-based trajectory model(GBTM)which is designed to identify groups of individuals following similar developmental trajectories was used to identify latent subgroups of individuals following a similar progression of FB.The primary outcomes were hospital mortality,organ dysfunction,major adverse kidney events(MAKE)and severe respiratory adverse events(SRAE).We used multivariable Cox or logistic regression analysis to assess the association between FB trajectories and clinical outcomes.Results:Nine hundred eighty-six patients met the inclusion criteria and were assigned to GBTM analysis,and three latent FB trajectories were detected.64(6.5%),841(85.3%),and 81(8.2%)patients were identified to have decreased,low,and high FB,respectively.Compared with low FB,high FB was associated with increased hospital mortality[hazard ratio(HR)=1.63,95%CI 1.22–2.17],organ dysfunction[odds ratio(OR)=2.18,95%CI 1.22–3.42],MAKE(OR=1.80,95%CI 1.04–2.63)and SRAE(OR=2.33,95%CI 1.46–3.71),and decreasing FB was significantly associated with decreased MAKE(OR=0.46,95%CI 0.29–0.79)after adjustment for potential covariates.Conclusion:Latent subgroups of septic patients followed a similar FB progression.These latent fluid trajectories were associated with clinical outcomes.The decreasing FB trajectory was associated with a decreased risk of hospital mortality and MAKE.

Effects of high-volume hemofiltration on alveolar- arterial oxygen exchange in patients with refractory septic shock

BACKGROUND：High-volume hemofiltration （HVHF） is technically possible in severe acute pancreatitis （SAP） patients complicated with multiple organ dysfunction syndrome （MODS）. Continuous HVHF is expected to become a beneficial adjunct therapy for SAP complicated with MODS. In this study, we aimed to explore the effects of fluid resuscitation and HVHF on alveolar- arterial oxygen exchange, the Acute Physiology and Chronic Health Evaluation II （APACHE II） score in patients with refractory septic shock. METHODS：A total of 89 refractory septic shock patients, who were admitted to ICU, the Provincial Hospital affiliated to Shandong University from August 2006 to December 2009, were enrolled in this retrospective study. The patients were randomly divided into two groups： fluid resuscitation （group A, n=41）, and fluid resuscitation plus high-volume hemofiltration （group B, n=48）, The levels of O2 content of central venous blood （CcvO2）, arterial oxygen content （CaO2）, alveolar-arterial oxygen pressure difference P（A-a）DO2, ratio of arterial oxygen pressure/alveolar oxygen pressure （PaO2/ PAO2）, respiratory index （RI） and oxygenation index （OI） were determined. The oxygen exchange levels of the two groups were examined based on the arterial blood gas analysis at different times （0, 24, 72 hours and 7 days of treatment） in the two groups. The APACHE II score was calculated before and after 7-day treatment in the two groups. The levels of CcvO2, CaO2 on day 7 in group A were significantly lower than those in group B （CcvO2：0.60±0.24 vs, 0.72±0.28, P〈0.05; CaO2：0.84±0.43 vs. 0.94±0.46, P〈0.05）. The level of oxygen extraction rate （O2ER） in group A on the 7th day was significantly higher than that in group B （ 28.7±2.4 vs. 21.7±3.4, P〈0.01）. The levels of P（A-a）DO2 and RI in group B on the 7th day were significantly lower than those in group A. The levels of PaO2/PAO2 and OI in group B on 7th day were significantly higher than those in group A （P〈0.05 or P〈0.01）. The APACHE II score in the two groups reduced gradually after 7-day treatment, and the APACHE II score on the 7th day in group B was significantly lower than that in group A （8.2±3.8 vs. 17.2±6.8, P〈0.01）. HVHF combined with fluid resuscitation can improve alveolar- arterial-oxygen exchange, decrease the APACHE II score in patients with refractory septic shock, and thus it increases the survival rate of patients.

Value of dynamic plasma cell-free DNA monitoring in septic shock syndrome: A case report

BACKGROUND Mortality due to septic shock is relatively high.The dynamic monitoring of plasma cell-free DNA(cfDNA)can guide the treatment of septic shock.CASE SUMMARY Herein,we present a typical case of septic shock syndrome caused by the bacilli Acinetobacter baumannii and Pantoea.The patient complained of abdominal pain,fever and chills upon admission to the Emergency Department.Marked decreases in white blood cells and procalcitonin(PCT)were observed after the patient received continuous renal replacement and extracorporeal membrane oxygenation.Plasma cfDNA levels were consistently high,peaking at 1366.40 ng/mL,as measured by a duplex real-time PCR assay with an internal control,which was developed as a novel method for the accurate quantification of cfDNA.The patient died of septic shock on HD 8,suggesting that cfDNA could be used to monitor disease progression more effectively than PCT and the other inflammatory factors measured in this case.CONCLUSION CfDNA may be a promising marker that complements other inflammatory factors to monitor disease progression in patients with septic shock.

Development of septic shock and prognostic assessment in critically ill patients with coronavirus disease outside Wuhan, China

BACKGROUND: The study aims to illustrate the clinical characteristics and development of septic shock in intensive care unit(ICU) patients confirmed with severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) infection, and to perform a comprehensive analysis of the association between septic shock and clinical outcomes in critically ill patients with coronavirus disease(COVID-19).METHODS: Patients confirmed with SARS-Co V-2 infection, who were admitted to the ICU of the Third People's Hospital of Shenzhen from January 1 to February 7, 2020, were enrolled. Clinical characteristics and outcomes were compared between patients with and without septic shock.RESULTS: In this study, 35 critically ill patients with COVID-19 were included. Among them, the median age was 64 years(interquartile range [IQR] 59-67 years), and 10(28.4%) patients were female. The median ICU length of stay was 16 days(IQR 8-23 days). Three(8.6%) patients died during hospitalization. Nine(25.7%) patients developed septic shock in the ICU, and these patients had a significantly higher incidence of organ dysfunction and a worse prognosis than patients without septic shock.CONCLUSIONS: Septic shock is associated with a poor outcome in critically ill COVID-19 patients and is one of the hallmarks of the severity of patients receiving ICU care. A dysregulated immune response, uncontrolled infl ammation, and coagulation disorders are strongly associated with the development and progression of COVID-19-related septic shock.

Correlation of Inferior Vena Cava Respiratory Variability Index with Central Venous Pressure and Hemodynamic Parameters in Ventilated Pigs with Septic Shock

Septic shock is a common critical condition, for which effective early fluid resuscitation is the therapeutic focus. According to the 2008 international guidelines for management of severe sepsis and septic shock, resuscitation should achieve a central venous pressure （CVP） of 8-12 mmHg within the first 6 h. However, it is still uncertain about the sensitivity and specificity of CVP in reflecting the cardiac preload. Ultrasonography is a simple, rapid, non-invasive, and repeatable method for the measurement of sensitivity and specificity of CVP and has thus gradually attracted the increasing attention of physicians. It was reported that ultrasonography can show the inferior vena cava diameter, respiratory variability index, and blood volume in patients with sepsis or heart failure.

Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

BACKGROUND: Triggering receptor expressed on myeloid cells-1(TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify infl ammation and serves as a critical mediator of infl ammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock.METHODS: We genotyped two TREM-1 single nucleotide polymorphisms(SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis.RESULTS: TREM-1 rs2234246 A allele in the promoter region was signifi cantly associated with the susceptibility of septic shock in recessive model(AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model(AG, OR=0.72, 95%CI 0.43–1.19, P=0.02; AA, OR=2.71, 95%CI 1.00–7.42; P=0.03). However, in three inherited models(dominant model, recessive model, and codominant model), none of the assayed loci was signif icantly associated with the prognosis of septic shock. The nonsurvivor group demonstrated higher plasma IL-6 levels(99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/m L, AG 85.4±43 pg/m L, and GG 65.3±30.7 pg/m L(P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were signifi cantly higher than those in patients with GG genotypes(P<0.01).CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.