Passive leg raising as an indicator of fluid responsiveness in patients with severe sepsis

In the management of critically ill patients, the assessment of volume responsiveness and the decision to administer a fluid bolus constitute a common dilemma for physicians. Static indices of cardiac preload are poor predictors of volume responsiveness. Passive leg raising （PLR） mimics an endogenous volume expansion （VE） that can be used to predict fluid responsiveness. This study was to assess the changes in stroke volume index （SVI） induced by PLR as an indicator of fluid responsiveness in mechanically ventilated patients with severe sepsis. This was a prospective study. Thirty-two mechanically ventilated patients with severe sepsis were admitted for VE in ICU of the First Affiliated Hospital, Zhejiang University School of Medicine and Ningbo Medical Treatment Center Lihuili Hospital from May 2010 to December 2011. Patients with non-sinus rhythm or arrhythmia, parturients, and amputation of the lower limbs were excluded. Measurements of SVI were obtained in a semi-recumbent position （baseline） and during PLR by the technique of pulse indicator continuous cardiac output （PiCCO） system prior to VE. Measurements were repeated after VE （500 mL 6% hydroxyethyl starch infusion within 30 minutes） to classify patients as either volume responders or non-responders based on their changes in stroke volume index （ASVI） over 15%. Heart rate （HR）, systolic artery blood pressure （ABPs）, diastolic artery blood pressure （ABPd）, mean arterial blood pressure （ABPm）, mean central venous pressure （CVPm） and cardiac index （CI） were compared between the two groups. The changes ofABPs, ABPm, CVPm, and SVI after PLR and VE were compared with the indices at the baseline. The ROC curve was drawn to evaluate the value of ASVI and the change of CVPm （ACVPm） in predicting volume responsiveness. SPSS 17.0 software was used for statistical analysis. Among the 32 patients, 22 were responders and 10 were non-responders. After PLR among the responders, some hemodynamic variables （including ABPs, ABPd, ABPm and CVPm） were significantly elevated （101.2±17.6 vs. 118.6±23.7, P=0.03; 52.8±10.7 vs. 64.8±10.7, P=0.006; 68.3±11.7 vs. 81.9±14.4, P=0.008; 6.8±3.2 vs. 11.9±4.0, P=0.001）. After PLR, the area under curve （AUC） and the ROC curve of ASVI and ACVPm for predicting the responsiveness after VE were 0.882±0.061 （95%CI 0.759-1.000） and 0.805±0.079 （95%CI 0.650-0.959） when the cut-off levels of ASVI and ACVPm were 8.8% and 12.7%, the sensitivities were 72.7% and 72.7%, and the specificities were 80% and 80%. Changes in ASVI and ACVPm induced by PLR are accurate indices for predicting fluid responsiveness in mechanically ventilated patients with severe sepsis.

The scoring system for patients with severe sepsis after orthotopic liver transplantation

BACKGROUND: Because of the complicated pathological features after liver transplantation, severe sepsis is difficult to treat and often leads to death. This study was undertaken to analyze the role of orthotopic liver transplantation (OLT) in patients with severe sepsis and to evaluate the effect of the scoring system. METHODS: Fifty-six patients conformed to the inclusion criteria. They were divided into two groups: non-OLT group (group A) and OLT group (group B). Besides the general data of the patients, the surveillance of blood lactate, the number of failed organs, acute physiology and chronic health evaluationⅡ(APACHEⅡ) and mutiple organ dysfunction score (MODS) were evaluated at the 1st, 3rd and 7th day after OLT. RESULTS: The mortality during hospitalization was 30% in the non-OLT group and 57.6% in the other group. The level of blood lactate at the 1st day of OLT increased more significantly in the OLT group than in the non-OLT group (P<0.01). It was decreased but higher than that in the non-OLT group in the seven days after OLT. The number of failed organs in the OLT group was greater than that in the non-OLT group (P<0.01). The continuous score of APACHEⅡwas not significantly different in the two groups. But the continuous MODS in the OLT group was higher than that in the non-OLT group (P<0.01), which was consistent with the number of failed organs. CONCLUSIONS: The persistently higher level of blood lactate during 7 days may be a dependent risk factor. Immunosuppression may be another risk factor for OLT patients. The mortality of OLT in patients with severe sepsis in 28 days is almost double that in non-OLT patients. The MODS score is better than the APACHEⅡscore in the assessment of organ failure in OLT patients with severe sepsis. The standard scoring system could be improved or a new scoring system that includes the blood lactate score should be established for liver transplantation.

Association of genetic variants in the IRAK-4 gene with susceptibility to severe sepsis

BACKGROUND:The association of genetic variation in the IRAK-1 gene with sepsis outcome has been proved.However,few studies have addressed the impact of the IRAK-4 gene variants on sepsis risk.This study aimed to determine whether the polymorphisms in the IRAK-4 gene are associated with susceptibility to and prognosis of severe sepsis in the Chinese Han ethnic population.METHODS:In this case-control study,192 patients with severe sepsis hospitalized in the emergency department of Zhongshan Hospital from February 2006 to December 2009 and 192healthy volunteers were enrolled.Exclusion criteria included metastatic tumors,autoimmune diseases,AIDS or treatment with immunosuppressive drugs.This study was approved by the ethical committee of Zhongshan Hospital,Fudan University.Sepsis patients were divided into a survival group(n=124)and a non-survival group(n=68)according to the 30-day mortality.Primer 3 software was used to design PCR and sequencing primers.Genomic DNA was extracted from peripheral blood mononuclear cells.Seven tagSNPs in IRAK-4 were selected according to the data of the Chinese Han population in Beijing from the Hapmap project and genotyped by direct sequencing.The chi-square test was used to evaluate the differences in genotype and allele frequencies between the two groups.RESULTS:The distributions of all tagSNPs were consistent with Hardy-Weinberg equilibrium.The allele and genotype frequencies of rs4251545(G/A)were significantly different between the severe sepsis and healthy control groups(P=0.015,P=0.035,respectively).Carriers of the rs4251545A had a higher risk for severe sepsis compared with carriers of the rs4251545G(OR=1.69,95%CI:1.10-2.58).The allele and genotype frequencies of all SNPs were not significantly different between the survival group and non-survival group.CONCLUSION:These findings indicate that the variants in IRAK-4 are significantly associated with susceptibility to severe sepsis in the Chinese Han ethnic population.

Research Progress of Continuous Blood Purification in the Treatment of Severe Sepsis in Children

Pediatric sepsis is the most common disease in pediatric critical illness,because the main reason for the disease is that children's immune level is not high or the immune system is not perfect,when children's lung,abdominal cavity and blood system are infected,it will cause systemic inflammation and immune dysfunction.Early clinical symptoms are mainly irregular and intermittent fever.When the disease develops to severe sepsis,the children will suffer from acute heart failure,oliguria,respiratory alkalosis and even multiple organ failure.The incidence of death is high.It is reported that the incidence rate of sepsis in children can reach 0.3%,and the mortality rate is 50%.High incidence rate,high mortality rate and high treatment cost are the biggest problems in the pediatric field.In the past,the clinical hope of clearing away heat and toxin,promoting blood circulation and removing stasis,strengthening inflammation and other methods in traditional Chinese medicine,but the treatment effect is not ideal.With the improvement of modem medical understanding of sepsis,continuous blood purification therapy is introduced into the treatment of children with severe sepsis.In order to further explore the effect of continuous blood purification in the treatment of children with severe sepsis,the author summarizes the clinical practice experience and relevant literature,hoping to provide reference for relevant medical staff。

Community-Acquired Severe Sepsis:A Prospective Cohort Study

Severe sepsis (SS) is one of the principal causes of admission in intensive care units (ICU), with an associated high morbidity and mortality. This study intends to characterize epidemiology of community-acquired SS (CASS) with special emphasis in the prevalence of multidrug resistant organisms and independent prognostic factors associated with ICU mortality. Methods: A prospective cohort study was conducted over 3.5 years, including all consecutive adult patients with CASS admitted to a mixed ICU, in a 600-bed university-affiliated hospital. Results: 1221 patients were admitted into the ICU, 25% with CASS. The mean age was 59 years and the mean SAPS (simplified acute physiological score) was II 48. Most had septic shock (67%). Respiratory (57%), intra-abdominal (22%) and urinary tract (8%) infections were the main sources of infection. The overall isolation rate was 56%. The most common identified microorganisms were Streptococcus pneumoniae (27%), Escherichia coli (22%), Staphylococcus aureus methicillin sensitive (8%) and Haemophilus influenzae (7%). The median ICU and hospital length of stay were 8 and 16 days, respectively. The ICU mortality rate was 33. Independent risk factors associated with higher mortality were older age, higher SAPS II, septic shock and chronic hepatic disease. Female gender was independently associated with lower mortality. The type of microorganism was not significantly associated with prognosis. Conclusion: CASS was highly prevalent among ICU admissions. Independent risk factors associated with ICU mortality included older age and previous comorbidities, but mainly severity of acute illness reinforcing the need for early recognition and treatment. Multidrug resistant organisms were implicated in considerable proportion of community-acquired sepsis.

Maternal Sepsis in Intensive Care Unit at Omdurman New Hospital-Tertiary Obstetric Facility, Khartoum-Sudan

Introduction: Sever sepsis and septic shock contributes to maternal morbidity and mortality. The etiology of sever sepsis and septic shock during pregnancy and postpartum result from obstetric related or non-obstetric related conditions. Objectives: It aimed to determine rate, characters, morbidity and mortality of septic obstetric cases at Omdurman New Hospital. Methods: It was a descriptive, prospective, analytic, cross-sectional hospital based total coverage study;conducted at Omdurman New Hospital (ONH), Khartoum-Sudan. Results: Sever sepsis and septic shock rate 1.16 (13/1124 = 1.16%) of hospital pregnancy complication admission. Hyperthermia, Tachycardia and hypotension are the main presenting clinical findings and uterine infection is the main focus of sepsis. The mean average Intensive Care Unit (ICU) stay is 6.3-day. Organs dysfunctions are the main morbidity and mortality is reported in five cases. Conclusion: Sever sepsis and septic shock contributes in maternal morbidity and mortality. Safe obstetric care prevents maternal sepsis and improves the outcome. Management of sever sepsis and septic shock remains a challenge in obstetric medicine.

Liver histology in ICU patients dying from sepsis:A clinico-pathological study

AIM:To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit. METHODS: Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded. RESULTS: Liver biochemistries were increased in the majority of patients before death. Histology of liver bi- opsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholan- gitis/cholangiolitis in 20% of patients. Mixed hepatitic/ cholestatic type of liver injury was observed in 6/15 (40%) patients and hepatitc in 9/15 (60%). Steatosis was ob- served in 11/15 (73.3%) patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was as- sociated with increased hospitalization in the ICU prior death (P = 0.026). CONCLUSION: Features of hepatitis and steatosis arethe main histological findings in the liver in the majority of patients dying from sepsis.

Treatment of patients with severe sepsis using Ulinastatin and Thymosin al： a prospective, randomized, controlled pilot study

Background Tradition treatment of sepsis and new therapies, including high dose corticosteroids and non-steroidal anti-inflammatory drugs, have proven unsuccessful in improving survival. This study aimed to evaluate the potential efficacy of immunomodulating therapy using Ulinastatin （UTI） plus Thymosin al （Tal） for improving organ function and reducing mortality in patients with severe sepsis. Methods A prospective study was carried out with randomized and controlled clinical analysis of 114 patients conforming to the enrollment standard. All patients had severe sepsis and received standard supportive care and antimicrobial therapy. Fifty-nine patients were also administered UTI plus Tal （defined as Group A）, 55 patients were given a placebo （defined as Group B）. Clinical parameters were determined by evaluation with the Acute Physiology and Chronic Health Evaluation II （APACHE II）, multiple organ failure （MOF） and the Glasgow Coma Scores （GCS） on entry and after therapy on the 3rd, 8th, and 28th day. By flow cytometery and ELISA lymphocyte subsets and cytokines were analyzed. Survival analysis was determined by the Kaplan-Meier method at 28, 60, and 90 days. Results Based on comparison of the two groups, patients in Group A exhibited a better performance in organ failure scores which was noticeable soon after initiation of treatment. Patients in Group A also demonstrated a better resolution of pre-existing organ failures during the observation period. After initiation of treatment, significant improvements in the CD4^＋/CD8^＋ ratio, a quicker balance between proinflammatory mediators such as tumor necrosis factor a, interleukin 6 and anti-inflammatory cytokines including interleukin 4 and interleukin 10 were found. This was followed by cumulative survival increases of 17.3% at 28 days, 28.9% at 60 days, and 31.4% at 90 days in Group A. The reduction in mortality was accompanied by a considerably shorter stay in the ICU and a shorter length of supportive ventilation, antimicrobial and dopamine therapy. Conclusion UTI plus Tal has a beneficial role in the treatment of severe sepsis.

Relationship between adrenal function and prognosis in patients with severe sepsis

Background It is known that the hypothalamic-pituitary-adrenal （HPA） axis is highlighted by stimulation, such as sepsis, trauma, etc, when corticortropin increases and plasma cortisol levels enhance. Relative adrenal insufficiency is not uncommon in critically ill patients and may occur in severe sepsis patients with high plasma cortisol levels. It has been demonstrated that a short corticotropin test has a good prognostic value and is helpful in identifying patients with septic shock at high risk for death, but it has not been established for all severe sepsis patients, especially in China. The aim of this study is to explore the relationship between adrenal function and prognosis in patients with severe sepsis. Methods This prospective study was conducted between July and December 2004 in 6 teaching hospitals. Two hundred and forty patients with severe sepsis were enrolled in this study. A short corticotropin stimulation test was performed in all patients by intravenous injection of 250 pg of corticotropin. Blood samples were taken immediately before the test （TO）, 30 （T30） and 60 （T60） minutes afterward, and the plasma cortisol concentration was measured by radio-immunoassay. At the onset of severe sepsis, the following parameters were recorded： age, sex, Acute Physiology and Chronic Health Evaluation （APACHE） II, heart rate, mean arterial pressure （MAP）, arterial partial pressure of oxygen （PaO2）/fraction of inspired oxygen （FiO2）, peripheral blood of hemoglobin, platelets and leukocyte concentration and the number of organ failure. Patients were designated into two groups （survival and non-survival groups） according to the 28-day mortality. Relative adrenal insufficiency was defined as the difference between TO and the highest value of T30 or T60 （△Tmax） ≤9 μg/dl. Results （1） Two hundred and forty patients with severe sepsis were included in this study, with 134 patients in the survival group and 106 in the non-survival group. The 28-day mortality was 44.2%. （2） Between the survival group and non-survival group age, APACHE II, peripheral blood of platelets, the number of organ failures, TO and ATmax showed significant differences. TO was （23±10） μg/dl and （36＋18） μg/dl in the survival group and nonsurvival group respectively. △Tmax was （18±9） and （10±8） μg/dl in the survival group and non-survival group respectively. The areas under the ROC curve for TO and ATmax were both 0.72, and the area under the ROC curve for APACHE II was 0.70. By multivariate analysis age, TO, the number of organ failures and relative adrenal insufficiency （△Tmax ≤9 μg/dl） were independent predictors of death. （3） The incidence of relative adrenal insufficiency was 38.3% in total, 19.4% in the survival group and 62.3% in the non-survival group （P〈0.001）. The 28-day mortality was 71.7% among the relative adrenal insufficiency patients but 27.0% among normal adrenal function patients. Conclusions The prevalence of relative adrenal insufficiency is high in severe sepsis. Relative adrenal insufficiency has a good prognostic value for severe sepsis.

Structured lipid emulsion as nutritional therapy for the elderly patients with severe sepsis

Background The nutritional support is one of the important therapeutic strategies for the elderly patients with severe sepsis,but there is controversial in choosing a parenteral nutrition formulation.This study was designed to compare the therapeutic effects of structured lipid emulsion,physically mixed medium,and long-chain fat emulsion in the treatment of severe sepsis in elderly patients.Methods A total number of 64 elder patients with severe sepsis were enrolled in the study.After a week of enteral nutritional support,the patients were randomly divided into research （structured lipid emulsion as parenteral alimentation） and control groups （physically mixed medium and long-chain fat emulsion as parenteral alimentation）.The alterations of plasma albumin,lipid metabolism,and blood glucose level were recorded after parenteral alimentation and were compared between the two groups.Results The plasma levels of albumin,prealbumin,cholesterol,and triglyceride were decreased in all the patients after one week of enteral nutritional support treatment （t=7.78,P=0.000; t=10.21,P=0.000; t=7.99,P=0.000; and t=10.99,P=0.000）.Further parenteral alimentation with different lipid emulsions had significant effects on the serum prealbumin and albumin （t=3.316,P=0.002; t=3.200,P=0.002）,whilst had no effects on the blood glucose and triglyceride level （t=7.78,P=0.000; t=4.228,P=0.000）.In addition,the two groups had a significantly different Apache Ⅱ score,ventilator time,and hospital stay time （t=-2.213,P=0.031;t=2.317,P=0.024; t=2.514,P=0.015）.Conclusions The structured lipid emulsion was safe as parenteral nutrition for elderly patients with severe sepsis.It was demonstrated to be superior to the physically mixed medium and long-chain fat emulsion with respect to the protein synthesis and prognosis.

SARS-CoV-2(COVID-19),viral load and clinical outcomes;lessons learned one year into the pandemic:A systematic review

BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections is diagnosed via real time reverse transcriptase polymerase chain reaction(RT-PCR)and reported as a binary assessment of the test being positive or negative.High SARS-CoV-2 viral load is an independent predictor of disease severity and mortality.Quantitative RT-PCR may be useful in predicting the clinical course and prognosis of patients diagnosed with coronavirus disease 2019(COVID-19).AIM To identify whether quantitative SARS-CoV-2 viral load assay correlates with clinical outcome in COVID-19 infections.METHODS A systematic literature search was undertaken for a period between December 30,2019 to December 31,2020 in PubMed/MEDLINE using combination of terms“COVID-19,SARS-CoV-2,Ct values,Log_(10) copies,quantitative viral load,viral dynamics,kinetics,association with severity,sepsis,mortality and infectiousness”.After screening 990 manuscripts,a total of 60 manuscripts which met the inclusion criteria were identified.Data on age,number of patients,sample sites,RT-PCR targets,disease severity,intensive care unit admission,mortality and conclusions of the studies was extracted,organized and is analyzed.RESULTS At present there is no Food and Drug Administration Emergency Use Authorization for quantitative viral load assay in the current pandemic.The intent of this research is to identify whether quantitative SARS-CoV-2 viral load assay correlates with severity of infection and mortality?High SARS-CoV-2 viral load was found to be an independent predictor of disease severity and mortality in majority of studies,and may be useful in COVID-19 infection in susceptible individuals such as elderly,patients with co-existing medical illness such as diabetes,heart diseases and immunosuppressed.High viral load is also associated with elevated levels of TNF-α,IFN-γ,IL-2,IL-4,IL-6,IL-10 and C reactive protein contributing to a hyper-inflammatory state and severe infection.However there is a wide heterogeneity in fluid samples and different phases of the disease and these data should be interpreted with caution and considered only as trends.CONCLUSION Our observations support the hypothesis of reporting quantitative RT-PCR in SARS-CoV-2 infection.It may serve as a guiding principle for therapy and infection control policies for current and future pandemics.

The surviving sepsis campaign： 2013 and beyond

The 2012 revision of the Surviving Sepsis Campaign.＂ International Guideless for Management of SevereSepsis and Septic Shock was recently published （February 2013） in Critical Care Medicine and Intensive Care Medicine.1,2 The effort to create this document occurred over two years and likely represents the most comprehensive buy-in of any international medical guidelines to date with 30 sponsoring organizations. Included in this list of sponsoring organizations is the Chinese Society of Critical Care Medicine-China Medical Association and the Chinese Society of Critical Care Medicine. The evidence based medicine （EBM） grading system continues to evolve under the leadership of the Grades of Recommendation Assessment Development and Evaluation Group （GRADE Group）, based in Canadal Each recommendation is graded based on quality of evidence and strength of recommendation.