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.

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.

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.

Influence of the Pre-shock State on the Prognosis of Medical Patients with Sepsis: A Retrospective Cohort Study

Objective To investigate the effects of the pre-shock state on the mortality of patients with sepsis.Methods We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state,and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates.Results A total of 303 patients(groups: sepsis 135 [44.6%]), pre-shock state(93 [30.7%]), and septic shock(75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group,but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points.Conclusion The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.

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.

Metabolic theory of septic shock

Septic shock is a life threatening condition that can develop subsequent to infection. Mortality can reach as high as 80% with over 150000 deaths yearly in the United States alone. Septic shock causes progressive failure of vital homeostatic mechanisms culminating in immunosuppression, coagulopathy and microvascular dysfunction which can lead to refractory hypotension, organ failure and death. The hypermetabolic response that accompanies a systemic inflammatory reaction places high demands upon stored nutritional resources. A crucial element that can become depleted early during the progression to septic shock is glutathione. Glutathione is chiefly responsible for supplying reducing equivalents to neutralize hydrogen peroxide, a toxic oxidizing agent that is produced during normal metabolism. Without glutathione, hydrogen peroxide can rise to toxic levels in tissues and blood where it can cause severe oxidative injury to organs and to the microvasculature. Continued exposure can result in microvascular dysfunction, capillary leakage and septic shock. It is the aim of this paper to present evidence that elevated systemic levels of hydrogen peroxide are present inseptic shock victims and that it significantly contributes to the development and progression of this frequently lethal condition.

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.

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.

Timing, method and discontinuation of hydrocortisone administration for septic shock patients

AIM To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes.METHODS This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone.It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31 st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic(ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects.RESULTS All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h(range, 47.5-90.5) vs 108 h(range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 μg/kg per minute(range, 0.11-0.28 μg)] compared with patients who were given bolus [0.34 μg/kg per minute(range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus(83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock(r = 0.80; P < 0.0001); ROC curve analysis revealed that the best criteria for prediction of shock reversal was a time to initiation of hydrocortisone of ≤ 13 h after administration of norepinephrine, with an area under the curve of 0.81(P < 0.001). The maximal dose of norepinephrine at initiation of hydrocortisone with the highest association with shock reversal was ≤ 0.28 μg/kg per minute, with an area under the curve of 0.75(P = 0.0002). On a logistic regression model, hydrocortisone taper was not associated with a lower risk of shock relapse(RR = 1.29; P = 0.17) but was related to a higher probability of hyperglycemia [odds ratio(OR), 5.3; P = 0.04] and hypokalemia(OR = 10.6; P = 0.01). CONCLUSION Continuous infusion of hydrocortisone could hasten the resolution of septic shock compared to bolus administration. Earlier initiation corresponds with a higher probability of shock reversal. Tapering strategy is unnecessary.

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.

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.

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.

Comparing the demographic data and outcomes of septic shock patients presenting to teaching or non-teaching metropolitan hospitals in the United States

BACKGROUND:Studies looking at the effect of hospital teaching status on septic shock related in-hospital mortality are lacking.The aim of this study was to examine the effect of hospital teaching status on mortality in septic shock patients in the United States.METHODS:This was a retrospective observational study,using the Nationwide Emergency Department Sample Database(released in 2018).All patients with septic shock were included.Complex sample logistic regression was performed to assess the impact of hospital teaching status on patient mortality.RESULTS:A total of 388,552 septic shock patients were included in the study.The average age was 66.93 years and 51.7%were males.Most of the patients presented to metropolitan teaching hospitals(68.2%)and 31.8%presented to metropolitan non-teaching hospitals.Septic shock patients presenting to teaching hospitals were found to have a higher percentage of medical comorbidities,were more likely to be intubated and placed on mechanical ventilation(50.5%vs.46.9%)and had a longer average length of hospital stay(12.47 d vs.10.20 d).Septic shock patients presenting to teaching hospitals had greater odds of in-hospital mortality compared to those presenting to metropolitan non-teaching hospitals(adjusted odd ratio[OR]=1.295,95%confidence interval[CI]:1.256-1.335).CONCLUSION:Septic shock patients presenting to metropolitan teaching hospitals had significantly higher risks of mortality than those presenting to metropolitan non-teaching hospitals.They also had higher rates of intubation and mechanical ventilation as well as longer lengths of hospital stay than those in non-teaching hospitals.

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.

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.

EFFECT OF INDOMETHACIN ON SEPTIC SHOCK:EXPERIMENTAL AND PRELIMINARY CLINICAL TRIALS

Twenty-four rabbits were randomly divided into two groups: indomethacin group (Group A, n=12) and control group (Group B, n=12). Rabbits in septic shock had profound hypotension, hypoxia, leukocytopenia, thrombocytopenia, increased levels of lactate and prostaniods. Indomethacin (3 mg/kg) given 10 minutes after the occurrence of shock significantly improved the 24-hour survival of animals, rapidly reversed the hypotensive state of shock, increased the arterial oxygen pressure, partly prevented the increase of blood lactate, and decreased the level of prostaniods. Preliminary clinical trials also showed that indomethacin decreased the level of prostaniods and raised the blood pressure in pediatric patients with septic shock. It is clear that further clinical study is warranted.

Unexplained septic shock after colonoscopy with polyethylene glycol preparation in a young adult:A case report

BACKGROUND Colonoscopy has become a routine physical examination as people’s health awareness has increased.Polyethylene glycol(PEG)is greatly used in bowel preparation before colonoscopy due to its price and safety advantages.Septic shock after colonoscopy with PEG preparation is extremely rare,with only very few cases in critically ill patients.Herein,we describe a case of septic shock in a healthy young adult immediately following colonoscopy with PEG preparation.CASE SUMMARY A 33-year-old young adult presented to our hospital for colonoscopy with PEG bowel preparation due to recurrent diarrhea for 7 years.The male's previous physical examination showed no abnormal indicators,and colonoscopy results were normal;however,he exhibited septic shock and markedly elevated white blood cell,C-reactive protein,and procalcitonin levels on the second day after colonoscopy.Immediate resuscitation and intensive care with appropriate antibiotics improved his condition.However,the blood and stool cultures did not detect the pathogen CONCLUSION Septic shock after colonoscopy is rare,especially in young adults.The authors considered the possibility of opportunistic infections after PEG bowel preparation,and clinicians should monitor patients for the possibility of such complications.