Cholecystokinin octapeptide improves cardiac function by activating Cholecystokinin octapeptide receptor in endotoxic shock rats

AIM: To explore the effect of sulfated cholecystokinin octapeptide (sCCK-8) on cardiac functions and its receptor mechanism in endotoxic shock (ES) rats. METHODS: The changes of the mean arterial pressure (MAP), heart rate (HR), the left ventricular pressure (LVP) and the maximal/minimum rate of LVP (±LVdp/dt max) were measured by using physiological record instrument in eight groups of rats. The expression of cholecystokinin-A receptor (CCK-AR) and cholecystokinin-B receptor (CCK-BR) mRNA of myocardium in ES rats was examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) Low doses of sCCK-8 (0.4 μg/kg) caused tachycardia (441±27, normal control 391±22 s/min) and slight increase in MAP, LVP and ±LVdp/dtmax (16.96±1.79, 18.21±1.69 and +768.85±31.28/-565.04±27.71 kPa, respectively, all P<0.01), while medium doses (4.0 μg/kg) and high doses of sCCK-8 (40 μg/kg) elicited bradycardia and marked increase in MAP, LVP and ±LVdp/dtmax (17.29±1.63, 19.46±2.57 and +831.46±22.57/-606.08 ±31.32; 17.46±1.08, 19.83±2.91 and +914.52±35.95/ -639.15±30.23 kPa, respectively, all P<0.01). Proglumide (1.0 mg/kg), a nonselective antagonist of CCK-receptor (CCK-R), significantly inhibited the pressor effects of sCCK-8 (15.96±1.38, 17.36±0.66 and +748.18±19.29/-512.12±14.39 kPa, respectively, all P<0.01), whilst reversing the bradycardiac responses. (2) High doses of LPS (8 mg/kg) elicited marked decrease in MAP, LVP and ±LVdp/dtmax. (7.16±0.59, 7.6±0.68 and +298.01±25.52/ -166.96±19.25 kPa, respectively, all P<0.01). Pretreatment with sCCK-8 (40 μg/kg) could reverse the decline of cardiac functions (10.71±0.45, 11.7±1.26 and +446.04±67.18/ -347.90±36.98 kPa, respectively, all P<0.01), while proglumide could cause further decline of cardiac function in ES rats (4.71±0.67, 5.58±1.25 and +226.48±15.84/ -142.83±20.23 kPa, respectively, all P<0.01). (3) CCK-A/BR mRNAs were expressed in myocardium of control rats. Gene expression of CCK-AR and CCK-BR significantly increased in myocardium of ES rats. The increase of CCK-AR mRNA induced by LPS began at 0.5 h, peaked at 2 h, kept a high level at 6 h and declined at 12 h, respectively. Similar to CCK-AR mRNA, the expression of CCK-BR mRNA peaked at 2 h and kept a high level at 6 h, but it did not change at the first 0.5 h and was stable at a high level at 12 h. CONCLUSION: The above results indicate that endogenous and exogenous sCCK-8 may significantly improve cardiac function and intractable hypotension of ES rats, which was likely related to high expression of CCK-A/BR in myocardium induced by LPS.

THE EFFECT OF ACUPUNCTURING ACUPOINTS ON THE CHANGE OF ELECTROENCEPHALOGRAM (EEG) IN ENDOTOXIC SHOCKED RATS

In present work,EEG and BP were used as the indexes to observe the relationbetween the change of EEG and the change of BP in the endotoxic shocked rats。At maintainingshock for 1 hr,dysrhythmia of EEG appeared in 38/46 cases.Simultaneously,there was a markeddrop in Bp,P【0.05.Following the shocked time prolonged,dysrhythmia was getting severe。AfterEA”Rengzhong"(n=14)or“Zusanli”(n=12),BP was significantly increased(P【0.05),anddysrhythmia of EEG showed clear improvement in most of the rats。There was a close relation be-tween the changes of EEG and BP,the change of EEG had a direct bearing on the change of BP.

EFFECTS OF METHYLENE BLUE ON THE BLOOD PRESSUREAND CGMP OF ENDOTOXIC SHOCK RABBITS

Objective To investigate the effect of methylene blue (MB) on the blood pressure and cGMP ofendotoxic shock. Methods An experiment was performed on 16 New Zealand rabbits suffering from endotoxicshock, in which 8 were distributed to the trial group (MB infusion) and another 8 to the control group (normalsaline). The mean arterial pressure (MAP), plasma cyclic monophosphate guanylate (cGMP), and arterialnatriuretic factor (ANF) in the two groups were observed. Results in the trial group MB infusion elevated MAP(P<0.01), decreased cGMP (P<0.01) and did not change the level of ANF. In the control group, normal salineinfusion did not alter MAP, plasma cGMP and ANF level. In addition, the MAP of the trial group was foundsignificantly higher than that of the control group (P<0.01) and the plasma cGMP of the trial group significantlylower than that of the control group (P<0.01). Conclusion These data suggest that the elevation of plasmacGMP is related to hypotension and MB in vivo can effectively inhibit soluable guanylate Cyclase, thus decreaseplasma cGMP level and increase MAP of rabbits with endotoxic shock. This indicates that MB can be used as adrug for the treatment of endotoxic shock.

Protective effects of bactericidal/permeability-increasing protein onrats after endotoxic shock

objective: To investigate the protective effects of bactericidal/permeability-increa protein (BPIP) on rats after endotoxic shock as to provide more experimental evidence for studies on its clinical use. Methods:E. coli 026:B6 LPS was injected at a dosage of 12. 5 mg/kg through the artery to reproduce endo toxic shock. BPIP at a dosage of 5 mg/kg (BPIP-treated group) or equal volume of normal saline (control group) were injected immediately after the injection of LPS. Results: ①Survival time of the shocked animals was prolonged and the 24 h survival rate was also significantly increased in BPIP-treated group as compared with the control group. ②The mean arterial pressure, left intraventricular systolic pressure, isovolemic ven tricular pressure and ±dp/dtmax. were significantly higher in BPIP-treated group than in control group. ③ Plasma levels of glutamic-pyruvic transaminase and urea nitrogen were markedly higher but those of endotox in and TNFα were lower in BPIP-treated group than in control group. Conclusion: BPIP can exert significant protective effects on cardiac, hepatic and renal functions in rats after endotoxic shock, indicating that BPIP might be a good choice in treatment of sepsis/septic shock.

Effect of flunixin meglumine alone and in combination on haemodynamics during bovine endotoxic shock and after treatment

To investigate the effect of Flunixin meglumine- a NSAID;alone and in combination with hypertonic saline on endotoxemic buffalo calves, two groups of five apparently healthy male buffalo calves aged be-tween 6-8 months were subjected to I.V. infusion of E.coli endotoxin at the rate of 5μg/kg BW per hour for 3 hours. A highly significant (P < 0.01) fall in mean systolic,diastolic, pulse, mean arterial pressure (M.A.P), central venous pressure (C.V.P) and haemo-globin was observed till the end of endotoxin infusion while respiratory rate was significantly elevated along with a non-significant alteration in rectal tem-perature and hematocrit during the infusion of en-dotoxin. Immediately at the end of endotoxin infusion, flunixin meglumine at the rate of 1.1 mg/kg B.W was infused i.v. in group-I animals and group-II animals were infused with hypertonic saline solution (H.S.S.) at the rate of 4 ml/Kg BW as one time infusion fol-lowed by flunixin meglumine at the rate of 1.1 mg/kg B.W which resulted in increase of various parameters either to normal or very close to normal value while the rectal temperature and haematocrit decreased non-significantly throughout the observation period of 7 hours. No improvement in Hb and respiration was observed consequent to FM administration. Both treatments successfully raised systolic, diastolic, pulse pressure, C.V.P & M.A.P to normal pre-infusion val-ues. From the results of the present investigation, it can be concluded that i.v. infusion of FM alone and in combination with hypertonic saline solution in en-dotoxemic buffalo calves effectively restores the various hemodynamic parameters close to normal pre-infusion values and it can be used as immediate resuscitation measure to provide the clinician valu-able time to plan further long term treatment.

Comparing 11 early warning scores and three shock indices in early sepsis prediction in the emergency department

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED).METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points.RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point.CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

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.

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.

Regulatory effects of phospholipase A_2 inhibitors on platelet activating factor in endotoxic shock in rabbits

The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits were randomized into 4 groups as follows : The normal control (NC) group consisted of 12 rabbits with sham injection . the endotoxic shork (ES) group of 31 rabbits, the chloquine pretreated (CQ) group of 16 rabbits receiving 3 mg/kg of chlorqouine and the dexamethasone-pretreated (DM) group of 10 rabbits receiving 5 mg/kg of dexamethasone. Blood was sampled before and 5 and 30 min, 1 ,3, 5 and 8 h after the administration of endotoxin for the determination of PLA2, platelet activating factor (PAF) , TXB2 and 6-keto-PGF1α. In addrtion, changes of mean arterial pressure (MAP) and respiratory rate (RR) were also carefully recorded. It was found that the activities of PLA2 and PAF and the levels of TXB2 and 6-keto-PGF1α. were significantly increased after the infusion of endotoxin. CQ and DM markedly suppressed the activities of PLA2 and PAF. The inhibition of CQ on TXB2 and 6-keto-PGF1α was greater than that of DM. Besides, CQ and DM could increase the survival rate of the animals from 48% to 75% (CQ group) and 70% (DM group). These findings suggest that PLA2 inhibitors such as CQ and DM can significantly attenuate the formation of shock mediators such as PLA2, PAF, TXB2 and 6-keto-PGF1α, and so improve the prognosis of the victims of endotoxic shock.

Gene Delivery of SOCS3 Protects Mice from Lethal Endotoxic Shock

Suppressor of cytokine signaling 3 （SOCS3） was reported as a feedback inhibitor of cytokine receptor signaling by inhibiting the JAK-STAT signal transduction pathway. We sought to test the anti-endotoxic septic shock effect of liposome mediated gene delivery of SOCS3 in a lethal endotoxic shock mouse model. BALB/c mice were injected intraperitoneally with 200μg pcDNA3.1-SOCS3 cationic liposomes, while pcDNA3.1-IL-10 and empty vector as positive and negative control respectively. Forty-eight hours after gene delivery, mice were challenged with 4 μg of E.coli 0127：B8 LPS and 18 mg D-GaIN administered i.p. 90 min later, serum TNF-α level was determined. Survival over the next 48 h was evaluated. Peritoneal macrophages from survival mice were stimulated in vitro with 1 μg/ml LPS for 18 h, and the supernatants were harvested for determination of the amount of TNF-α. We found that gene delivery of SOCS3 significantly increase the mouse survival rate from 27.8 ± 9.6% of control group to 61.1 ± 9.6% （p 〈 0.01）. In comparison with control group （218 ± 13 pg/ml） and sham delivery group （219 ± 22 pg/ml）, gene delivery of SOCS3 reduced the level of serum TNF-α （68 ± 9 pg/ml） significantly （p 〈 0.01）. Furthermore, gene delivery of SOCS3 displayed the capacity of prevention of tolerance of peritoneal macrophages to LPS. These findings suggest that gene delivery of SOCS3 mediated by liposome is a promising approach for endotoxic septic shock treatment. Cellular ＆ Molecular Immunology.

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.

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.

Machine learning in data abstraction: A computable phenotype for sepsis and septic shock diagnosis in the intensive care unit

BACKGROUND With the recent change in the definition(Sepsis-3 Definition)of sepsis and septic shock,an electronic search algorithm was required to identify the cases for data automation.This supervised machine learning method would help screen a large amount of electronic medical records(EMR)for efficient research purposes.AIM To develop and validate a computable phenotype via supervised machine learning method for retrospectively identifying sepsis and septic shock in critical care patients.METHODS A supervised machine learning method was developed based on culture orders,Sequential Organ Failure Assessment(SOFA)scores,serum lactate levels and vasopressor use in the intensive care units(ICUs).The computable phenotype was derived from a retrospective analysis of a random cohort of 100 patients admitted to the medical ICU.This was then validated in an independent cohort of 100 patients.We compared the results from computable phenotype to a gold standard by manual review of EMR by 2 blinded reviewers.Disagreement was resolved by a critical care clinician.A SOFA score≥2 during the ICU stay with a culture 72 h before or after the time of admission was identified.Sepsis versions as V1 was defined as blood cultures with SOFA≥2 and Sepsis V2 was defined as any culture with SOFA score≥2.A serum lactate level≥2 mmol/L from 24 h before admission till their stay in the ICU and vasopressor use with Sepsis-1 and-2 were identified as Septic Shock-V1 and-V2 respectively.RESULTS In the derivation subset of 100 random patients,the final machine learning strategy achieved a sensitivity-specificity of 100%and 84%for Sepsis-1,100%and 95%for Sepsis-2,78%and 80%for Septic Shock-1,and 80%and 90%for Septic Shock-2.An overall percent of agreement between two blinded reviewers had a k=0.86 and 0.90 for Sepsis 2 and Septic shock 2 respectively.In validation of the algorithm through a separate 100 random patient subset,the reported sensitivity and specificity for all 4 diagnoses were 100%-100%each.CONCLUSION Supervised machine learning for identification of sepsis and septic shock is reliable and an efficient alternative to manual chart review.

Precision medicine in sepsis and septic shock:From omics to clinical tools

Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes.As it is associated with an increased risk of death,patients with this condition are candidates for receipt of a very well-structured and protocolized treatment.All patients should receive the fundamental pillars of sepsis management,which are infection control,initial resuscitation,and multiorgan support.However,specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms.Herein,we will review the framework for identifying subpopulations of patients with sepsis,septic shock,and multiorgan dysfunction who may benefit from specific therapies.Some of these approaches are still in the early stages of research,while others are already in routine use in clinical practice,but together will help in the effective generation and safe implementation of precision medicine in sepsis.

Shock index of patients with sepsis after continuous blood purification treatment and its relationship with systemic inflammatory response syndrome and immune response

Objective:To study the shock index of patients with sepsis after continuous blood purification (CBP) treatment and its relationship with systemic inflammatory response syndrome and immune response.Methods:A total of 88 patients with sepsis who underwent continuous blood purification treatment in our hospital between June 2012 and May 2016 were chosen as research subjects, shock index (SI) was compared before and after the treatment, and according to the level of SI after treatment, all patients were divided into shock group (n=27) with SI>0.5 points and no shock group (n=61) with SI≤0.5 points. Serum contents of inflammatory mediators, Th1/Th2 cellular immunity indexes, immunoglobulin and complement were compared between two groups of patients after treatment.Results: The level of SI in patients with sepsis was significantly lower than that before treatment. Serum contents of inflammatory mediators PCT, CRP and HMGB1 in no shock group were lower than those in shock group, contents of Th1 cytokines IL-2 and IFN-γ were higher than those in shock group, contents of Th2 cytokines IL-10 and IL-13 were lower than those in shock group, and contents of IgG, IgM, IgA, C3 and C4 were higher than those in shock group.Conclusion: The level of SI decreases in the patients with sepsis after CBP treatment, and SI level is directly correlated with the systemic inflammatory response syndrome and immune response levels.

Effect of CD11a／CD18 monoclonal antibody on the microcirculation disorder of rabbits in endotoxic shock

The CD11a/CD18 monoclonal antibody was injected into rabbits with endotoxic shock in order to observe the effect of the antibody on microcirculation. The resuh showed that the injection of CD11a/CD18 monoclonal antibody could obviously reduce the number of leukocytes adhered on the venule wall, increase the blood velocity and attenuate the falling of mean arterial pressure in the shock rabbits, which indicates that CD11a/CD18 takes part in the pathogenesis of leukocytes adherence in endotoxic shock. Blocking CD11a/CD18 can improve microcirculation to a certain extent.

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.

Adjuvant Administration of Vitamin C Improves Mortality of Patients with Sepsis and Septic Shock: A Systems Review and Meta-Analysis

The aim of this study was to examine whether vitamin C reduced mortality when adjutant therapy of patients with septic shock and severe sepsis compared with placebo by meta-analysis. Eligible trials were identified from Pubmed, Embase, Ovid, and the Cochrane database. Four randomized controlled trials (RCT) and two retrospective studies were published between 2000 and 2017 met the inclusion criteria and suitable for meta-analysis. The data were analyzed with randomized-effects or fixed-effects models using Review Manager Version 5.3. Four randomized studies with a total of 109 participants were suitable for meta-analysis. The heterogeneity was assessed by calculating the Q and I2 methods. A random-effects approach instead of a fixed-effects analysis was undertaken if I2 > 50%. Adjuvant vitamin C did not associate with a reduction in mortality as compared with placebo, it is occurred similarly in both RCT studies and retrospective studies. However, high doses of vitamin C (>50 mg/kg/day) significant reduced the mortality rate of severe sepsis patients. And administration of high doses of vitamin C to therapy severe sepsis did not significantly reduce the ICU length of stay. The results suggested a trend toward reducing mortality in severe sepsis and septic shock patients’ adjuvant with vitamin C. Further multicenter large randomized controlled trials are necessary to determine the potential benefits of vitamin C in patients with severe sepsis and septic shock.

Septic shock 3.0 criteria application in severe COVID-19 patients:An unattended sepsis population with high mortality risk

BACKGROUND Coronavirus disease 2019(COVID-19)can be associated with life-threatening organ dysfunction due to septic shock,frequently requiring intensive care unit(ICU)admission,respi-ratory and vasopressor support.There-fore,clear clinical criteria are pivotal for early recognition of patients more likely to need prompt organ support.Although most patients with severe COVID-19 meet the Sepsis-3.0 criteria for septic shock,it has been increasingly recognized that hyperlactatemia is frequently absent,possibly leading to an underestimation of illness severity and mortality risk.AIM To identify the proportion of severe COVID-19 patients with vasopressor support requirements,with and without hyperlactatemia,and describe their clinical outcomes and mortality METHODS We performed a single-center prospective cohort study.All adult patients admitted to the ICU with COVID-19 were included in the analysis and were further divided into three groups:Sepsis group,without both criteria;Vasoplegic Shock group,with persistent hypotension and vasopressor support without hyperlactatemia;and Septic Shock 3.0 group,with both criteria.COVID-19 was diagnosed using clinical and radiologic criteria with a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)positive RT-PCR test.RESULTS 118 patients(mean age 63 years,87%males)were included in the analysis(n=51 Sepsis group,n=26 Vasoplegic Shock group,and n=41 Septic Shock 3.0 group).SOFA score at ICU admission and ICU length of stay were different between the groups(P<0.001).Mortality was significantly higher in the Vasoplegic Shock and Septic Shock 3.0 groups when compared with the Sepsis group(P<0.001)without a significant difference between the former two groups(P=0.713).The log rank tests of Kaplan-Meier survival curves were also different(P=0.007).Ventilator-free days and vasopressor-free days were different between the Sepsis vs Vasoplegic Shock and Septic Shock 3.0 groups(both P<0.001),and similar in the last two groups(P=0.128 and P=0.133,respectively).Logistic regression identified the maximum dose of vasopressor therapy used(AOR 1.046;95%CI:1.012-1.082,P=0.008)and serum lactate level(AOR 1.542;95%CI:1.055-2.255,P=0.02)as the major explanatory variables of mortality rates(R20.79).CONCLUSION In severe COVID-19 patients,the Sepsis 3.0 criteria of septic shock may exclude approximately one third of patients with a similarly high risk of a poor outcome and mortality rate,which should be equally addressed.

Correlation between shock index and inflammation, oxidative stress as well as target organ damage in patients with sepsis

Objective:To study the correlation between shock index and inflammation, oxidative stress as well as target organ damage in patients with sepsis.Methods: A total of 70 patients with sepsis treated in our hospital between March 2013 and May 2016 were collected and divided into no shock group (SI<0.5) (n=11), general shock group (0.5 SI 2) (n=42) and severe shock group (SI>2.0) (n=17) according to the shock index (SI). Immediately after admission, serum levels of inflammatory factors, oxidative stress indexes and liver function indexes were detected.Results:Serum interleukin-1β (IL-1β), interleukin-8 (IL-8), tumor necrosis factor (TNF-α), advanced oxidation protein products (AOPPs), total bilirubin (TB),γ-glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) levels of severe shock group and general shock group were higher than those of no shock group while anti-inflammatory factors interleukin-10 (IL-10), interleukin-13 (IL-13), soluble tumor necrosis factor receptorⅠ(sTNF-RI), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and catalase (CAT) levels were lower than those of no shock group;serum IL-1β, IL-8, TNF-α, AOPPs, TB, GGT and ALT levels of severe shock group were higher than those of general shock group while IL-10, IL-13, sTNF-RI, CAT, GSH-Px and SOD levels were lower than those of general shock group.Conclusion:The higher the shock index in patients with sepsis, the more severe the inflammation, oxidative stress and target organ damage, and the two are positively correlated.