Pentraxin 3 (PTX3) Is Associated with Severe Sepsis and Fatal Disease in Emergency Room Patients with Suspected Infection: A Prospective Cohort Study

Background

Early diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection.

Methods

The study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA).

Results

The median PTX3 levels in groups 1–5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUC^ROC in the prediction of severe sepsis was 0.73 (95% CI 0.66–0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58–0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders.

Conclusions

A high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection.     

Predictors and Outcome of Hypoxemia in Severely Malnourished Children under Five with Pneumonia: A Case Control Design

Background

There is lack of information in the medical literature on predictors of hypoxemia in severely malnourished children with pneumonia, although hypoxemia is common and is often associated with fatal outcome in this population. We explored the predictors of hypoxemia in under-five children who were hospitalized for the management of pneumonia and severe acute malnutrition (SAM).

Methods

In this unmatched case-control design, SAM children of both sexes, aged 0–59 months, admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) with radiological pneumonia and hypoxemia during April 2011 to April 2012 were studied. SAM children with pneumonia and hypoxemia (SpO₂<90%) constituted the cases (n = 37), and randomly selected SAM children with pneumonia but without hypoxemia constituted controls (n = 111).

Results

The case-fatality was significantly higher among the cases than the controls (30% vs. 4%; p<0.001). In logistic regression analysis, after adjusting for potential confounders such as nasal flaring, head nodding, inability to drink, and crackles in lungs, fast breathing (95% CI = 1.09–13.55), lower chest wall in-drawing (95% CI = 2.48–43.41), and convulsion at admission (95% CI = 3.14–234.01) were identified as independent predictors of hypoxemia in this population. The sensitivity of fast breathing, lower chest wall in-drawing and convulsion at admission and their 95% confidence intervals (CI) to predict hypoxemia were 84 (67–93)%, 89 (74–96)%, and 19 (9–36)% respectively, and their specificity were 53 (43–63)%, 60 (51–69)% and 98 (93–100)% respectively.

Conclusion and Significance

Fast breathing and lower chest wall in-drawing were the best predictors of hypoxemia in SAM children with pneumonia. There thus, in resources poor settings where pulse oximetry is not available, identification of these simple clinical predictors of hypoxemia in such children could be reliably used for early O₂ supplementation in addition to other appropriate management to reduce morbidity and deaths.     

Reducing Deaths from Severe Pneumonia in Children in Malawi by Improving Delivery of Pneumonia Case Management

Objective

To evaluate the pneumonia specific case fatality rate over time following the implementation of a Child Lung Health Programme (CLHP) within the existing government health services in Malawi to improve delivery of pneumonia case management.

Methods

A prospective, nationwide public health intervention was studied to evaluate the impact on pneumonia specific case fatality rate (CFR) in infants and young children (0 to 59 months of age) following the implementation of the CLHP. The implementation was step-wise from October 1^st 2000 until 31^st December 2005 within paediatric inpatient wards in 24 of 25 district hospitals in Malawi. Data analysis compared recorded outcomes in the first three months of the intervention (the control period) to the period after that, looking at trend over time and variation by calendar month, age group, severity of disease and region of the country. The analysis was repeated standardizing the follow-up period by using only the first 15 months after implementation at each district hospital.

Findings

Following implementation, 47,228 children were admitted to hospital for severe/very severe pneumonia with an overall CFR of 9•8%. In both analyses, the highest CFR was in the children 2 to 11 months, and those with very severe pneumonia. The majority (64%) of cases, 2–59 months, had severe pneumonia. In this group there was a significant effect of the intervention Odds Ratio (OR) 0•70 (95%CI: 0•50–0•98); p = 0•036), while in the same age group children treated for very severe pneumonia there was no interventional benefit (OR 0•97 (95%CI: 0•72–1•30); p = 0•8). No benefit was observed for neonates (OR 0•83 (95%CI: 0•56–1•22); p = 0•335).

Conclusions

The nationwide implementation of the CLHP significantly reduced CFR in Malawian infants and children (2–59 months) treated for severe pneumonia. Reasons for the lack of benefit for neonates, infants and children with very severe pneumonia requires further research.     

Post-Discharge Mortality in Children with Severe Malnutrition and Pneumonia in Bangladesh

Background

Post-discharge mortality among children with severe illness in resource-limited settings is under-recognized and there are limited data. We evaluated post-discharge mortality in a recently reported cohort of children with severe malnutrition and pneumonia, and identified characteristics associated with an increased risk of death.

Methods

Young children (<5 years of age) with severe malnutrition (WHO criteria) and radiographic pneumonia on admission to Dhaka Hospital of icddr,b over a 15-month period were managed according to standard protocols. Those discharged were followed-up and survival status at 12 weeks post-discharge was determined. Verbal autopsy was requested from families of those that died.

Results

Of 405 children hospitalized with severe malnutrition and pneumonia, 369 (median age, 10 months) were discharged alive with a follow-up plan. Of these, 32 (8.7%) died in the community within 3 months of discharge: median 22 (IQR 9–35) days from discharge to death. Most deaths were reportedly associated with acute onset of new respiratory or gastrointestinal symptoms. Those that died following discharge were significantly younger (median 6 [IQR 3,12] months) and more severely malnourished, on admission and on discharge, than those that survived. Bivariate analysis found that severe wasting on admission (OR 3.64, 95% CI 1.66–7.97) and age <12 months (OR 2.54, 95% CI 1.1–8.8) were significantly associated with post-discharge death. Of those that died in the community, none had attended a scheduled follow-up and care-seeking from a traditional healer was more common (p<0.001) compared to those who survived.

Conclusion and Significance

Post-discharge mortality was common in Bangladeshi children following inpatient care for severe malnutrition and pneumonia. The underlying contributing factors require a better understanding to inform the potential of interventions that could improve survival.     

Variations in Mortality in Children Admitted with Pneumonia to Kenyan Hospitals

Background

The existing case fatality estimates of inpatient childhood pneumonia in developing countries are largely from periods preceding routine use of conjugate vaccines for infant immunization and such primary studies rarely explore hospital variations in mortality. We analysed case fatality rates of children admitted to nine Kenyan hospitals with pneumonia during the era of routine infant immunization with Hib conjugate vaccine to determine if significant variations exist between hospitals.

Methods

Pneumonia admissions and outcomes in paediatric wards are described using data collected over two time periods: a one-year period (2007–2008) in nine hospitals, and data from a 9.25-year period (1999-March 2008) in one of the participating hospitals. Hospital case fatality rates for inpatient pneumonia during 2007 to 2008 were modeled using a fixed effect binomial regression model with a logit link. Using an interrupted time series design, data from one hospital were analysed for trends in pneumonia mortality during the period between 1997 and March 2008.

Results

Overall, 195 (5.9%) children admitted to all 9 hospitals with pneumonia from March 2007 to March 2008 died in hospital. After adjusting for child’s sex, comorbidity, and hospital effect, mortality was significantly associated with child’s age (p<0.001) and pneumonia severity (p<0.001). There was evidence of significant variations in mortality between hospitals (LR χ² = 52.19; p<0.001). Pneumonia mortality remained stable in the periods before (trend −0.03, 95% CI −0.1 to 0.02) and after Hib introduction (trend 0.04, 95% CI −0.04 to 0.11).

Conclusions

There are important variations in hospital-pneumonia case fatality in Kenya and these variations are not attributed to temporal changes. Such variations in mortality are not addressed by existing epidemiological models and need to be considered in allocating resources to improve child health.     

Burden of Severe Pneumonia,Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates

The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3–3.9 million) episodes of severe pneumonia and 0.35 million (0.31–0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49–0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92–119 thousand) pneumococcal deaths occurred in India. The top contributors to India’s pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our results highlight the need to improve access to care and increase coverage and equity of pneumonia preventing vaccines in states with high pneumonia burden.     

Mortality Predictors in Renal Transplant Recipients with Severe Sepsis and Septic Shock

Introduction

The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock.

Methods

Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality.

Results

A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51±13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16–23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6–2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ≤1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7–19.6; p = 0.004), delta SOFA 24 h (OR = 1.7; 95% CI, 1.2–2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8–102.2; p<0.0001), hematologic dysfunction (OR = 6.8; 95% CI, 2.0–22.6; p = 0.002), admission from the ward (OR = 3.4; 95% CI, 1.2–9.7; p = 0.02) and acute kidney injury stage 3 (OR = 5.7; 95% CI,1.9–16.6; p = 0.002).

Conclusions

Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction.     

Do Children with Uncomplicated Severe Acute Malnutrition Need Antibiotics? A Systematic Review and Meta-Analysis

Background

Current (1999) World Health Organization guidelines recommend giving routine antibiotics (AB) for all children with severe acute malnutrition (SAM), even if they have uncomplicated disease with no clinically obvious infections. We examined the evidence behind this recommendation.

Methods and Findings

OVID-MEDLINE, EMBASE, COCHRANE, GLOBAL-HEALTH, CINAHL, POPLINE, AFRICA-WIDE-NiPAD, and LILACS were searched for AB efficacy, bacterial resistance, and infection rates in SAM. Following PRISMA guidelines, a systematic review and meta-analysis were performed. Three randomised controlled trials (RCT), five Cochrane reviews, and 37 observational studies were identified. One cohort-study showed no increase in nutritional-cure and mortality in uncomplicated SAM where no AB were used. (p>0.05). However, an unpublished RCT in this setting did show mortality benefits. Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27–55%) vs 22% (IQR 17–23%) and population-weighted-means 52.9% (range 23–57%) vs 35.4% (range 6.7–42%). Susceptibilities to second-line AB were better, above 80%. Prevalence of serious infections in SAM, pooled from 24 studies, ranged from 17% to 35.2%. No study infered any association of infection prevalence with AB regimens in SAM.

Conclusions

The evidence underlying current antibiotic recommendations for uncomplicated SAM is weak. Susceptibility-studies favour amoxicillin over cotrimoxazole. However, given that these antibiotics have side-effects, costs, and risks as well as benefits, their routine use needs urgent testing. With reliable monitoring, we believe that there is sufficient equipoise for placebo controlled RCTs, the only robust way to demonstrate true efficacy.     

Hydroxyethyl Starch (HES 130/0.4) Impairs Intestinal Barrier Integrity and Metabolic Function: Findings from a Mouse Model of the Isolated Perfused Small Intestine

BackgroundThe application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine.MethodsAn isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-to-pyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups.ResultsCompared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces.ConclusionA vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small intestine.     

限制性液体复苏与常规液体复苏对失血性休克患者临床疗效分析

目的:探讨限制性液体复苏与常规液体复苏对失血性休克患者死亡率、凝血功能及并发症的影响。方法:选取失血性休克患者100例,随机分为限制组(n=55)和常规组(n=45),其中限制组采用限制性液体复苏抗休克,而常规组采用常规液体复苏。比较两组患者输液量及死亡率、血压与检验指标、并发症发生率。结果:与常规组相比,限制组患者输液量较少,死亡率较低,痊愈率较高,差异有统计学意义(P0.05)。与常规组相比,限制组患者平均动脉压、碱剩余明显较低,血红蛋白、血小板、红细胞比容明显较高,凝血酶原时间明显较短,差异有统计学意义(P0.001)。与常规组相比,限制组患者急性呼吸窘迫综合征、多器官功能障碍综合征发生率较低,差异有统计学意义(P0.05)。结论:限制性液体复苏为失血性休克患者赢得更多后续急诊手术止血时间,能降低患者死亡率和并发症如急性呼吸窘迫综合征、多器官功能障碍综合征的发生率。     

液体复苏对于严重脓毒症患者生存率的预后分析

目的:严重脓毒症中液体复苏的生理病理学理论支持及动物实验证据不足,有必要进行相关临床试验来确定液体复苏对于严重脓毒症患者预后的影响。方法:将26名严重脓毒症和脓毒症休克患者分为液体复苏组和非液体复苏组。比较两组的28天生存率,ICU住院天数的差别,对两组在院生存天数进行生存函数分析。结果:液体复苏组的28天生存率为41.7%,未液体复苏组的28天生存率为50.0%,之间没有统计学差异(P=0.713)。液体复苏组的平均住院天数为24.7±6.0天,未液体复苏组的平均住院天数为17.7±3.4天,两组之间没有统计学差异(P=0.308)。液体复苏组的中位在院生存天数为38.0[28.0,48.0],液体复苏组的中位在院生存天数为25.0[22.8,27.2]。两组之间有显著统计学差异,(Log Rank P=0.044,Breslow P=0.025)。结论:在严重脓毒症及脓毒症休克患者中,采取液体复苏能够延长患者的中位在院生存天数,可见液体复苏在严重脓毒症的治疗中有重要意义。尚未发现液体复苏能提高严重脓毒症患者28天生存率的相关证据。采取液体复苏究竟能否改善严重脓毒症患者预后,还需要大样本随机临床对照试验来证明。     

Incidence and Characteristics of Acute Kidney Injury in Severe Diabetic Ketoacidosis

Aims

Acute kidney injury is a classical complication of diabetic ketoacidosis. However, to the best of our knowledge, no study has reported the incidence and characteristics of acute kidney injury since the consensus definition was issued.

Methods

Retrospective study of all cases of severe diabetic ketoacidosis hospitalised consecutively in a medical surgical tertiary ICU during 10 years. Patients were dichotomised in with AKI and without AKI on admission according to the RIFLE classification. Clinical and biological parameters were compared in these populations. Risk factors of presenting AKI on admission were searched for.

Results

Ninety-four patients were included in the study. According to the RIFLE criteria, 47 patients (50%) presented acute kidney injury on admission; most of them were in the risk class (51%). At 12 and 24 hours, the percentage of AKI patients decreased to 26% and 27% respectively. During the first 24 hours, 3 patients needed renal replacement therapy. Acute renal failure on admission was associated with a more advanced age, SAPS 2 and more severe biological impairments. Treatments were not different between groups except for insulin infusion. Logistic regression found 3 risk factors of presenting AKI on admission: age (odds ratio 1.060 [1.020–1.100], p<0.01), blood glucose (odds ratio 1.101 [1.039–1.166], p<0.01) and serum protein (odds ratio 0.928 [0.865–0.997], p = 0.04).

Conclusions

Acute kidney injury is frequently associated with severe diabetic ketoacidosis on admission in ICU. Most of the time, this AKI is transient and characterised by a volume-responsiveness to fluid infusion used in DKA treatment. Age, blood glucose and serum protein are associated to the occurrence of AKI on ICU admission.     

High Rates of Pneumonia in Children under Two Years of Age in a South East Asian Refugee Population

Background

There are an estimated 150 million episodes of childhood pneumonia per year, with 11–20 million hospital admissions and 1.575 million deaths. Refugee children are particularly vulnerable, with poorly defined pneumonia epidemiology.

Methods

We followed a birth cohort of 955 refugee infants, born over a one-year period, until two years of age. Clinical and radiographic pneumonia were diagnosed according to WHO criteria. Detailed characteristics were collected to determine risk factors for clinical, radiological and multiple episodes of pneumonia. Investigations were taken during a pneumonia episode to help determine or to infer an aetiological diagnosis.

Findings

The incidence of clinical pneumonia was 0.73 (95% CI 0.70–0.75) episodes per child year (/CY) and of radiological primary endpoint pneumonia (PEP) was 0.22/CY (95% CI 0.20–0.24). The incidence of pneumonia without severe signs was 0.50/CY (95% CI 0.48–0.53), severe pneumonia 0.15/CY (95% CI 0.13–0.17) and very severe pneumonia 0.06/CY (0.05–0.07). Virus was detected, from a nasopharyngeal aspirate, in 61.3% of episodes. A reduced volume of living space per person (IRR 0.99, 95% CI 0.99–1.0, p = 0.003) and young maternal age (IRR 1.59, 95% CI 1.12–2.27, p = 0.01) were risk factors for developing pneumonia. The risk of a child having >1 episode of pneumonia was increased by having a shorter distance to the next house (IRR 0.86, 95% CI 0.74–1.00, p = 0.04). Infants were at risk of having an episode of PEP if there was a shorter distance from stove to bed (IRR 0.89, 95% CI 0.80–0.99, p = 0.03). Raised CRP and neutrophil values were associated with PEP.

Conclusions

There was a high incidence of pneumonia in young children in this SE Asian refugee population. Viral infections were important, however CXR and non-specific marker findings suggested that bacteria may be involved in up to a third of cases.     

Translating Resuscitation Guidelines into Practice: Health Care Provider Attitudes,Preferences and Beliefs Regarding Pediatric Fluid Resuscitation Performance

Introduction

Children who require fluid resuscitation for the treatment of shock present to tertiary and non-tertiary medical settings. While timely fluid therapy improves survival odds, guidelines are poorly translated into clinical practice. The objective of this study was to characterize the attitudes, preferences and beliefs of health care providers working in acute care settings regarding pediatric fluid resuscitation performance.

Methods

A single-centre survey study was conducted at McMaster Children''s Hospital from January to May, 2012. The sampling frame (n = 115) included nursing staff, physician staff and subspecialty trainees working in Pediatric Emergency Medicine (PEM) or Pediatric Critical Care Medicine (PCCM). A self-administered questionnaire was developed and assessed for face validity prior to distribution. Eligible participants were invited at 0, 2, and 4 weeks to complete a web-based version of the survey. A follow-up survey administration phase was conducted to improve the response rate.

Results

Response rate was 72.2% (83/115), with 83% (68/82) self-identifying as nursing staff and 61% (50/82) as PCCM providers. Resuscitation experience, frequency of shock management, and years in specialty, were similar between PCCM and PEM responders. Physicians and nurses had differing opinions regarding the most effective method to achieve rapid fluid resuscitation in young children presenting in shock (p<0.001). Disagreement also existed regarding the age and size of patients in whom rapid infuser devices, such as the Level-1 Rapid Infuser, should be used (p<0.001). Providers endorsed a number of potential concerns related to the use of rapid infuser devices in children, and only 14% of physicians and 55% of nursing staff felt that they had received adequate training in the use of such devices (p = 0.005).

Conclusions

There is a lack of consensus among health care providers regarding how pediatric fluid resuscitation guidelines should be operationalized, supporting a need for further work to define best practices.     

脓毒症患儿预后的影响因素分析及pSOFA评分、PCIS评分及早期血乳酸测定的预测价值探讨

摘要 目的：分析脓毒症患儿预后的影响因素,并探讨儿科序贯器官衰竭评估（pSOFA）评分、小儿危重病例评分法（PCIS）评分及早期血乳酸（Lac）测定对预后的预测价值。方法：选取2020年1月～2022年5月我院儿童医学中心收治的107例脓毒症患儿,根据脓毒症患儿28 d生存情况分为死亡组48例和存活组59例。收集患儿临床资料,对患儿进行pSOFA评分、PCIS评分评价和血Lac检测。采用单因素和多因素Logistic回归分析脓毒症患儿死亡的影响因素,受试者工作特征（ROC）曲线分析pSOFA评分、PCIS评分和血Lac水平对脓毒症患儿死亡的预测价值。结果：107例脓毒症患儿28 d死亡率为44.86％（48/107）。死亡组脓毒症分级、合并器官损伤≥3个比例、机械通气比例、pSOFA评分、白细胞计数、D-二聚体、C反应蛋白、降钙素原、血Lac水平高于存活组,机械通气时间长于存活组,PCIS评分、血小板计数、白蛋白水平低于存活组（P＜0.05）。多因素Logistic回归分析显示,严重脓毒症、脓毒性休克、合并≥3个器官损伤、机械通气、pSOFA评分增加、D-二聚体升高、血Lac升高为脓毒症患儿死亡的独立危险因素,PCIS评分增加、白蛋白升高为独立保护因素（P＜0.05）。ROC曲线分析显示,pSOFA评分、PCIS评分和血Lac水平联合预测脓毒症患儿死亡的曲线下面积大于各指标单独预测。结论：脓毒症分级、合并器官损伤、机械通气、D-二聚体、白蛋白、pSOFA评分、PCIS评分、血Lac为脓毒症患儿预后的影响因素,pSOFA评分、PCIS评分和血Lac水平联合预测脓毒症患儿死亡风险的价值较高。     

The Role of Whole Blood Impedance Aggregometry and Its Utilisation in the Diagnosis and Prognosis of Patients with Systemic Inflammatory Response Syndrome and Sepsis in Acute Critical Illness

Objective

To assess the prognostic and diagnostic value of whole blood impedance aggregometry in patients with sepsis and SIRS and to compare with whole blood parameters (platelet count, haemoglobin, haematocrit and white cell count).

Methods

We performed an observational, prospective study in the acute setting. Platelet function was determined using whole blood impedance aggregometry (multiplate) on admission to the Emergency Department or Intensive Care Unit and at 6 and 24 hours post admission. Platelet count, haemoglobin, haematocrit and white cell count were also determined.

Results

106 adult patients that met SIRS and sepsis criteria were included. Platelet aggregation was significantly reduced in patients with severe sepsis/septic shock when compared to SIRS/uncomplicated sepsis (ADP: 90.7±37.6 vs 61.4±40.6; p<0.001, Arachadonic Acid 99.9±48.3 vs 66.3±50.2; p = 0.001, Collagen 102.6±33.0 vs 79.1±38.8; p = 0.001; SD ± mean)). Furthermore platelet aggregation was significantly reduced in the 28 day mortality group when compared with the survival group (Arachadonic Acid 58.8±47.7 vs 91.1±50.9; p<0.05, Collagen 36.6±36.6 vs 98.0±35.1; p = 0.001; SD ± mean)). However haemoglobin, haematocrit and platelet count were more effective at distinguishing between subgroups and were equally effective indicators of prognosis. Significant positive correlations were observed between whole blood impedance aggregometry and platelet count (ADP 0.588 p<0.0001, Arachadonic Acid 0.611 p<0.0001, Collagen 0.599 p<0.0001 (Pearson correlation)).

Conclusions

Reduced platelet aggregometry responses were not only significantly associated with morbidity and mortality in sepsis and SIRS patients, but also correlated with the different pathological groups. Whole blood aggregometry significantly correlated with platelet count, however, when we adjust for the different groups we investigated, the effect of platelet count appears to be non-significant.     

脓毒症患儿血清SAA、PCT、CRP水平与预后的关系及其诊断价值分析

摘要 目的：探讨脓毒症患儿血清淀粉样蛋白A（SAA）、降钙素原（PCT）、C反应蛋白（CRP）与预后的关系,并分析三者对脓毒症的诊断价值。方法：纳入我院于2016年8月～2020年6月期间收治的脓毒症患儿60例开展回顾性研究,作为脓毒症组,选取同期于我院进行体检的健康儿童40例作为对照组,比较两组血清SAA、PCT、CRP水平。根据脓毒症患儿1个月内的生存、死亡情况,分成生存组（n=42）、死亡组（n=18）,比较两组临床资料及血清SAA、PCT、CRP水平,经COX回归模型分析脓毒症患儿死亡的危险因素。绘制受试者工作特征（ROC）曲线分析血清SAA、PCT、CRP对脓毒症的诊断价值。结果：脓毒症组血清SAA、PCT、CRP水平显著高于对照组（P＜0.05）。死亡组器官障碍数量＞2个、脓毒性休克患儿占比分别为55.56%、44.44%,显著高于生存组的19.05%、9.52%（P＜0.05）;死亡组入院后1 h内使用抗菌治疗患儿占比为38.89%,显著低于生存组的69.05%（P＜0.05）;死亡组血清SAA、PCT、CRP水平高于生存组（P＜0.05）。COX多因素分析结果显示,器官障碍数量＞2、脓毒性休克及血清SAA、PCT、CRP水平升高是脓毒症患儿死亡的危险因素（P＜0.05）,而入院后1 h内使用抗菌治疗是脓毒症患儿死亡风险的保护性因素（P＜0.05）。血清SAA、PCT、CRP单独及三者联合诊断脓毒症的曲线下面积（AUC）分别为0.808、0.780、0.761、0.912。结论：脓毒症患儿血清SAA、PCT、CRP明显升高,三者升高均为脓毒症患儿死亡的危险因素,且对脓毒症具有一定诊断价值。     

The Diagnostic and Prognostic Accuracy of Five Markers of Serious Bacterial Infection in Malawian Children with Signs of Severe Infection

Background

Early recognition and prompt and appropriate antibiotic treatment can significantly reduce mortality from serious bacterial infections (SBI). The aim of this study was to evaluate the utility of five markers of infection: C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), CD163 and high mobility group box-1 (HMGB1), as markers of SBI in severely ill Malawian children.

Methodology and Principal Findings

Children presenting with a signs of meningitis (n = 282) or pneumonia (n = 95), were prospectively recruited. Plasma samples were taken on admission for CRP, PCT, sTREM-1 CD163 and HMGB1 and the performance characteristics of each test to diagnose SBI and to predict mortality were determined. Of 377 children, 279 (74%) had SBI and 83 (22%) died. Plasma CRP, PCT, CD163 and HMGB1 and were higher in HIV-infected children than in HIV-uninfected children (p<0.01). In HIV-infected children, CRP and PCT were higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and PCT and CD163 were higher in non-survivors (p = 0.001, p = 0.05 respectively). In HIV-uninfected children, CRP and PCT were also higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and CD163 was higher in non-survivors (p = 0.05). The best predictors of SBI were CRP and PCT, and areas under the curve (AUCs) were 0.81 (95% CI 0.73–0.89) and 0.86 (95% CI 0.79–0.92) respectively. The best marker for predicting death was PCT, AUC 0.61 (95% CI 0.50–0.71).

Conclusions

Admission PCT and CRP are useful markers of invasive bacterial infection in severely ill African children. The study of these markers using rapid tests in a less selected cohort would be important in this setting.     

住院儿童肺炎发病情况及病毒病原学分析

目的:统计我院1-7岁住院儿童肺炎发病情况并进行病毒病原学分析。方法:收集2015年1月到2017年12月河北省人民医院1-7岁住院儿童8532例的临床资料,统计不同年龄段的肺炎患儿、重症肺炎患儿的发病情况及不同季节肺炎分布特点,统计不同病毒病原体住院肺炎儿童入院时的症状或体征情况,记录住院肺炎儿童并发症发生情况。结果:8532例住院儿童中,肺炎患儿2476例。1岁患儿肺炎、重症肺炎的发病率均最高,分别为54.67%(703/1286)、1.14%(8/703);7岁患儿肺炎发病率最低,为12.52%(126/1006);6岁和7岁重症肺炎发病率均为0.00%。冬季肺炎发病率最高,为33.38%(724/2169),春季、夏季、秋季发病率相当。病毒病原学显示,至少1种病毒检测阳性的有2061例,阳性率为83.24%。腺病毒和偏肺病毒阳性患儿出现发热、呼吸急促和呼吸困难的比例高于其他病毒感染;各种病毒阳性病例中,咳嗽、咳痰、流涕等呼吸道症状出现的频率相当。住院肺炎患儿中出现并发症以呼吸衰竭为主,占比为21.16%,其次是心力衰竭,占比为14.82%,脓毒血症的发生率为8.72%,其他并发症发生率均较低。结论:2015-2017年我院1-7岁住院儿童肺炎和重症肺炎的发生率以1岁最高,且随着年龄的增长发病率呈下降趋势,冬季最多见,病毒病原体中以腺病毒和偏肺病毒感染导致的发热、呼吸急促和呼吸困难症状较多,并发症以呼吸衰竭为主。     

Validity of Antibodies in Lymphocyte Supernatant in Diagnosing Tuberculosis in Severely Malnourished Children Presenting with Pneumonia

BackgroundThe diagnosis of tuberculosis (TB) in young children can be challenging, especially in severely malnourished children. There is a critical need for improved diagnostics for children. Thus, we sought to evaluate the performance of a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children presenting with suspected pneumonia.MethodsChildren less than 5 years with severe acute malnutrition and radiological features of pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh, were enrolled consecutively following informed written consent. In addition to clinical and radiological assessment, samples taken for TB diagnosis included gastric lavage fluid and induced sputum for microbiological confirmation. ALS was measured from venous blood, and results were evaluated in children classified as “confirmed”, “non-confirmed TB” or “not TB”.ResultsAmong 224 children who had ALS analysis, 12 (5.4%) children had microbiologically “confirmed TB”, a further 41 (18%) had clinically diagnosed “non-confirmed TB” and the remaining 168 (75%) were considered not to have TB. ALS was positive in 89 (40%) and negative in 85 (39%) of children, with a large number (47 or 21%) reported as “borderline”. These proportions were similar between the three diagnostic groups. The sensitivity and specificity of ALS when comparing “Confirmed TB” to “Not TB” was only 67% (95% CI: 31–91%) and 51% (95% CI: 42–60%), respectively.

Conclusions and Significance

Our data suggest that ALS is not sufficiently accurate to improve the diagnosis of TB in children with severe malnutrition.