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.

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.

Predictive value of thrombocytopenia for bloodstream infection in patients with sepsis and septic shock

BACKGROUND Thrombocytopenia is common in patients with sepsis and septic shock.AIM To analyse the decrease in the number of platelets for predicting bloodstream infection in patients with sepsis and septic shock in the intensive care unit.METHODS A retrospective analysis of patients admitted with sepsis and septic shock in Xingtai People Hospital was revisited.Patient population characteristics and laboratory data were collected for analysis.RESULTS The study group consisted of 85(39%)inpatients with bloodstream infection,and the control group consisted of 133(61%)with negative results or contamination.The percentage decline in platelet counts(PPCs)in patients positive for pathogens[57.1(41.3-74.6)]was distinctly higher than that in the control group[18.2(5.1–43.1)](P<0.001),whereas the PPCs were not significantly different among those with gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.Using receiver operating characteristic curves,the area under the curve of the platelet drop rate was 0.839(95%CI:0.783-0.895).CONCLUSION The percentage decline in platelet counts is sensitive in predicting bloodstream infection in patients with sepsis and septic shock.However,it cannot identify gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.

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.

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.

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.

Combining Serum Procalcitonin Level,Thromboelastography,and Platelet Count to Predict Short-term Development of Septic Shock in Intensive Care Unit

Objective Despite the recent advances in diagnosis and treatment,sepsis continues to lead to high morbidity and mortality.Early diagnosis and prompt treatment are essential to save lives.However,most biomarkers can only help to diagnose sepsis,but cannot predict the development of septic shock in high-risk patients.The present study determined whether the combined measurement of procalcitonin(PCT),thromboelastography(TEG)and platelet(PLT)count can predict the development of septic shock.Methods A retrospective study was conducted on 175 septic patients who were admitted to the intensive care unit between January 2017 and February 2021.These patients were divided into two groups:73 patients who developed septic shock were assigned to the septic shock group,while the remaining 102 patients were assigned to the sepsis group.Then,the demographic,clinical and laboratory data were recorded,and the predictive values of PCT,TEG and PLT count for the development of septic shock were analyzed.Results Compared to the sepsis group,the septic shock group had statistically lower PLT count and TEG measurements in the R value,K value,αangle,maximum amplitude,and coagulation index,but had longer prothrombin time(DT),longer activated partial thromboplastin time(APTT),and higher PCT levels.Furthermore,the Sequential Organ Failure Assessment(SOFA)score was higher in the septic shock group.The multivariate logistic regression analysis revealed that PCT,TEG and PLT count were associated with the development of septic shock.The area under the curve analysis revealed that the combined measurement of PCT,TEG and PLT count can be used to predict the development of septic shock with higher accuracy,when compared to individual measurements.Conclusion The combined measurement of PCT,TEG and PLT count is a novel approach to predict the development of septic shock in high-risk patients.

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.

Klebsiella pneumoniae invasive liver abscess syndrome with purulent meningitis and septic shock: A case from China's Mainland

@Yun Qian$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Chi-Chun Wong$Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong!Hong Kong, China@San-Chuan Lai$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Zheng-Hua Lin$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Wei-Liang Zheng$Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Hui Zhao$Emergency Department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Kong-Han Pan$Department of Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Shu-Jie Chen$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province, China@Jian-Min Si$Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University!Hangzhou 310016, Zhejiang Province, China$Institute of Gastroenterology, Zhejiang University!Hangzhou 310016, Zhejiang Province,

Pancreatic injury in patients with septic shock: A literature review

Sepsis and septic shock are life threatening condition associated with high mortality rate in critically-ill patients. This high mortality is mainly related to the inadequacy between oxygen delivery and cellular demand leading to the onset of multiorgan dysfunction. Whether this multiorgan failure affect the pancreas is not fully investigated. In fact, pancreatic injury may occur because of ischemia, overwhelming inflammatory response, oxidative stress, cellular apoptosis and/or metabolic derangement. Increased serum amylase and/or lipase levels are common in patients with septic shock. However, imaging test rarely reveal significant pancreatic damage. Whether pancreatic dysfunction does affect the prognosis of patients with septic shock or not is still a matter of debate. In fact, only few studies with limited sample size assessed the clinical relevance of the pancreatic injury in this group of patients. In this review, we aimed to describe the epidemiology and the physiopathology of pancreatic injury in septic shock patients, to clarify whether it requires specific management and to assess its prognostic value. Our main finding is that pancreatic injury does not significantly affect the outcome in septic shock patients. Hence, increased serum pancreatic enzymes without clinical features of acute pancreatitis do not require further imaging investigations and specific therapeutic intervention.

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.

Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock

The mixed venous-to-arterial carbon dioxide(CO_2)tension difference[P(v-a) CO_2]is the difference between carbon dioxide tension(PCO_2) in mixed venous blood(sampled from a pulmonary artery catheter) and the PCO_2 in arterial blood.P(v-a) CO_2 depends on the cardiac output and the global CO_2 production,and on the complex relationship between PCO_2 and CO_2 content.Experimental and clinical studies support the evidence that P(v-a) CO_2 cannot serve as an indicator of tissue hypoxia,and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO_2generated by the peripheral tissues.P(v-a) CO_2 can be replaced by the central venous-to-arterial CO_2 difference(△PCO_2),which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and,therefore,more easy to obtain at the bedside.Determining the △PCO_2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation(SCVO_2) > 70%associated with elevated blood lactate levels.Because high blood lactate levels is not a discriminatory factor in determining the source of that stress,an increased △PCO_2(> 6 mmHg)could be used to identify patients who still remain inadequately resuscitated.Monitoring the △PCO_2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and,thus,guiding the therapy.In this respect,it can aid to titrate inotropes to adjust oxygen delivery to CO_2 production,or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO_2 related to metabolic demand.The combination of P(v-a) CO_2 or △PCO_2 with oxygen-derived parameters through the calculation of the P(v-a) CO_2 or △PCO_2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism.

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.

Ulcerative colitis complicated with colonic necrosis, septic shock and venous thromboembolism: A case report

BACKGROUND Severe total colonic necrosis,septic shock and venous thromboembolism secondary to ulcerative colitis (UC) are rare and life-threatening.No such severe complications have been reported in the literature.CASE SUMMARY We report a 36-year-old woman who developed total colonic necrosis and septic shock secondary to UC.The patient was treated with emergency surgery because computed tomography showed suspicious perforations.Persistent massive ascites occurred after operation and computed tomography angiography demonstrated portal vein,mesenteric vein and splenic vein thrombosis.The patient was discharged from hospital after active treatment.CONCLUSION Clinicians should pay attention to venous thrombosis,colonic necrosis and septic shock in UC patients.Close observation of surgical indications and timely surgical intervention are the key to reduce mortality and complications in UC.

Noninvasive hemodynamic monitoring of septic shock in children

Septic shock in children is associated with high mortality and morbidity. Its management is time-sensitive and must be aggressive and target oriented. The use of clinical assessment alone to differentiate between cold and warm shock and to select the appropriate inotropic and vasoactive medications is fraught with errors. Semiquantitative and quantitative assessment of the preload,contractility and afterload using non-invasive tools has been suggested,in conjunction with clinical and laboratory assessment,to direct shock management and select between vasopressors,vasodilators and inotropes or a combination of these drugs. This review aims to describe non-invasive tools to assess the hemodynamic status in septic shock including echocardiography,trans-thoracic/trans-esophageal Doppler and electrical cardiometry. As septic shock is a dynamic condition that changes markedly overtime,frequent or continuous measurement of the cardiac output(CO),systemic vascular resistance(SVR) and other hemodynamic parameters using the above-mentioned tools is essential to personalize the treatment and adapt it over time. The different combinations of blood pressure,CO and SVR serve as a pathophysiological framework to manage fl-uid therapy and titrate inotropic and vasoactive drugs. Near infrared spectroscopy is introduced as a noninvasive method to measure end organ perfusion and assess the response to treatment.

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.

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.