Sequential Organ Failure Research Articles

2303 Trauma-related acute respiratory distress syndrome (ARDS) in India: Current incidence and management strategies

OBJECTIVES/SPECIFIC AIMS: Aim 1: To determine the true incidence of trauma-related acute respiratory distress syndrome (ARDS) in India. We propose to perform a prospective observational study to determine the incidence of ARDS in India. Aim 2: To perform a preliminary assessment of risk factors for ARDS in the Indian trauma population. We will leverage these findings against the global ARDS data to provide a foundation for further interventional studies. Aim 3: To evaluate the current management strategies and patient outcomes from ARDS in trauma subjects admitted to the Jai Prakash Narayan Apex Trauma Center (JPNATC). These findings will identify areas in need of practice-based performance improvement in ARDS therapies in India. METHODS/STUDY POPULATION: This application proposes an observational study of trauma patients with ARDS, a population that continues to have substantial in-hospital mortality. The approximate number of ICU-admitted trauma cases for the study period is 1700. Specific data elements to be collected include patient demographics, comorbidities, mechanism of injury, Injury Severity Score, risk factors for ARDS, sequential organ failure and assessment scores, vital signs, laboratory values, and evidence-based treatments received, including mechanical ventilation and adjunctive therapies. Outcome data will include discharge location, ICU and hospital length of stay and all-cause mortality. Selection of Subjects: We will include all patients admitted to the JPNATC Trauma and Neurosurgical ICUs intubated and mechanically ventilated and meeting the definition of Berlin definition of ARDS8. We will collect data for a total of 12 months. RESULTS/ANTICIPATED RESULTS: Due to gaps in reporting, the incidence, mortality, and practice-based management algorithms applied in trauma patients suffering from ARDS in India is unknown. We hypothesize that the overall incidence of trauma-related ARDS is higher, and the fraction of patients managed with evidence-based therapies is lower than global reported averages. DISCUSSION/SIGNIFICANCE OF IMPACT: Although the true incidence of ARDS in trauma subjects in India is currently unknown, we suspect that it is much higher than reported. Such data are important in identification of resource allocation including ICU bed and mechanical ventilator availability, particularly in a resource-limited environment. This proposal will aid in the development of research infrastructure at JPNATC, contribute to capacity building, and the establishment of a Clinical Research unit at the Apex Institute. Finally, a provision to develop a consortium and trauma quality improvement program among the existing trauma centers in New Delhi to disseminate important research findings and guidance to the rest of India is a future benefit of the study.

Elevated serum levels of lipoprotein‑associated phospholipaseA2 predict mortality rates in patients with sepsis.

Sepsis remains one of the leading contributors to mortality rates in the intensive care unit (ICU) and emergency intensive care unit (EICU). Therefore, any treatments against the agents which produce sepsis in a medical emergency, are welcome. Elevated serum levels of lipoprotein‑associated phospholipase A2 (Lp‑PLA2) have been reported in a small cohort of patients with inflammation. The present study evaluated serum levels of Lp‑PLA2 in patients with sepsis and investigated the role of Lp‑PLA2 in sepsis. The investigation involved the selection of 151patients with sepsis admitted to the emergency department of the Affiliated Hospital of Nantong University (Nantong, China) and 30 healthy controls. All patients (39 with sepsis, 55 with severe sepsis and 57 with septic shock) were examined on admission to the EICU. A complete blood count was performed, and serum levels of Lp‑PLA2, C‑reactive protein, procalcitonin, and interleukin 6, sequential organ failure (SOFA) scores and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were determined on hospital admission. The EICU and overall mortality rates were evaluated at baseline. The present study also assessed various laboratory parameters, clinical data and inflammatory cytokines. The patient follow up duration was 90days. The data suggested that the serum levels of Lp‑PLA2 on admission to the EICU in patients with sepsis were elevated, compared with those in healthy controls. The concentrations of Lp‑PLA2 were correlated with the severity of disease, and were significantly associated with experimental markers of inflammation and established prognostic scores. In the total cohort, persistently elevated levels of Lp‑PLA2 on admission for EICU treatment was a predictor of poor prognosis, and provided superior diagnostic use, compared with the prognostic scoring systems, including SOFA or APACHE II scores. Taken together, the results suggested that Lp‑PLA2, with respect to other markers of inflammation, may have a role as a prognostic marker in sepsis, and provide background evidence for further trials to evaluate the clinical and pathophysiologic roles of Lp‑PLA2 in sepsis. Persistently elevated serum concentrations of Lp‑PLA2 indicated an unfavorable outcome in patients with sepsis. In addition, the results indicated the potential role of Lp‑PLA2 as a prognostic biomarker in patients with sepsis during the early course of EICU treatment.

Organ dysfunction as a new standard for defining sepsis.

Despite advances in intensive care and the widespread use of standardized care included in the Surviving Sepsis Campaign Guidelines, sepsis remains a leading cause of death, and the prevalence of sepsis increases concurrent with the aging process. The diagnosis of sepsis was originally based on the evidence of persistent bacteremia (septicemia) but was modified in 1992 to incorporate systemic inflammatory response syndrome (SIRS). Since then, SIRS has become the gold standard for the diagnosis of sepsis. In 2016, the Society of Critical Care Medicine and the European Society of Intensive Care Medicine published a new clinical definition of sepsis that is called Sepsis-3. In contrast to previous definitions, Sepsis-3 is based on organ dysfunctions and uses a sequential organ failure (SOFA) score as an index. Thus, patients diagnosed with respect to Sepsis-3 will inevitably represent a different population than those previously diagnosed. We assume that this drastic change in clinical definition will affect not only clinical practice but also the viewpoint and focus of basic research. This review intends to summarize the pathophysiology of sepsis and organ dysfunction and discusses potential directions for future research.

Nobiletin: A Citrus Isolate to Make Sepsis Less Sour

Septic shock remains a major concern in critically ill patients. Morbidity, as reflected by cardiovascular instability and sequential organ failure, is high and mortality ranges from 20 to 50 % [1]. Treatment options are scarce and mainly causeoriented and symptomatic. Substantial efforts to control the coordinate but sometimes profuse and potentially lethal sepsis-induced immuno-inflammatory response remained unsuccessful. Indeed, large studies investigating numerous “magic bullets” interfering with sepsis-related immuneinflammatory or coagulation processes failed to show efficacy on relevant outcome parameters [2–4]. Also, the theoretical benefit of blood purification by restoring immune homeostasis through indiscriminate removal of inflammatorymediators could not be confirmed [5]. In this context, the paper of Li et al. is highly welcomed. The authors convincingly demonstrate a protective effect of nobiletin, a citrus flavone present in the peels of tangerine, mandarin and oranges, in murine endotoxic shock [6]. Interestingly, apart from inhibiting the “usual pro-inflammatory suspects” tumor necrosis factor-α and interleukin (IL)-6, the study focuses on two key protagonists within the sepsis cascade: high mobility group box-1 (HMGB-1) protein and nuclear factor kappa B (NF-κB) [6]. HMGB-1 is a late mediator of endotoxin lethality [7] and perfectly fits all criteria for an “alarmin” [8]. Alarmins form the endogenous branch of the larger family of damage-associated molecular patterns (DAMPs) that are released by threatened, injured, or necrotic cells [9]. In the nucleus, HMGB-1 stabilizes nucleosome formation and facilitates transcription factor binding. Outside the cell, it functions as a cytokine with weak direct pro-inflammatory activity [10] but considerable ability for indirect triggering of inflammation [11]. HMGB-1, indeed, acts as a potent chemoattractant for neutrophils, monocytes, macrophages, and dendritic cells and engages, among others, Toll-like, IL-1, and receptors for advanced glycation end-products (RAGE) that sustain or enhance the inflammatory process. Moreover, HMGB-1 and endotoxin synergistically reinforce each other at both receptor level and in activating transcriptional responses [11]. Severe sepsis [12] and acute inflammatory lung injury [13] are associated with lifethreatening out-of-control HMGB-1 responses. Thus, it makes perfect sense that measures for keeping the HMGB-1 release in check may dramatically influence the course of sepsis. Inhibiting HMGB-1 in murine sepsis protected against development of organ injury and reversed lethality [14]. Nosaka et al. recently showed that administration of amonoclonal antibody against HMGB1 suppressed the immuno-inflammatory response and significantly improved severe lung injury and survival in patients affected with H1N1 influenza A virus [15]. HMGB-1 is also effectively cleared by highly adsorptive dialysis membranes such as the acrylonitrile 69 surface-treated filter [16] which is increasingly used for continuous renal replacement therapy (CRRT) in hemodynamically unstable septic patients [17]. Though obviously an attractive and more easily available alternative for counteracting the noxious effects of HMGB1, clinical efficacy and benefit of such CRRT approach has not yet been established. 1 ICU Deparment, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium 2 ICU Deparment, UZ Brussel—VUB University, 101, Laarbeeklaan, 1090 Jette Brussels, Belgium 3 To whom correspondence should be addressed at ICU Deparment, UZ Brussel—VUB University, 101, Laarbeeklaan, 1090 Jette Brussels, Belgium. E-mail: Patrick.Honore@az.vub.ac.be

Transcriptomic correlates of organ failure extent in sepsis

Sepsis is characterised by the frequent presence of organ failure and marked immunologic alterations. We studied the association between the extent of organ failure and the transcriptomic response of septic patients. Gene expression profiles in the blood of 74 surgical patients with sepsis were compared with those of 30 surgical patients with no sepsis. Differentially expressed genes were assessed for their correlation with the sequential organ failure (SOFA) score. The expression levels of a group of genes participating in the cell cycle (HIST1H1C, CKS2, CCNA2, CDK1, CCNB2, CIT, CCNB1, AURKA, RAD51), neutrophil protease activity (ELANE, ADORA3, MPO, MMP8, CTSG), IL-1R and IL-18R response correlated directly with SOFA and mortality. Genes involved in T cell (LCK, CD3G, CD3D, ZAP70, ICOS, CD3E, CD28, IL2RB, CD8B, CD8A, CD40LG, IL23A, CCL5, SH2D1A, ITK, CD247, TBX21, GATA3, CCR7, LEF1, STAT4) and NK cell immunity (CD244, KLRK1, KLRD1) were inversely associated with SOFA and mortality. The extent of organ failure in sepsis correlates directly with the existence of imbalanced innate and adaptive responses at the transcriptomic level. Quantification of the expression levels of the genes identified here could contribute to the simultaneous assessment of disease severity and immunological alterations in sepsis.

Predictive modelling of survival and length of stay in critically ill patients using sequential organ failure scores.

The length of stay of critically ill patients in the intensive care unit (ICU) is an indication of patient ICU resource usage and varies considerably. Planning of postoperative ICU admissions is important as ICUs often have no nonoccupied beds available. Estimation of the ICU bed availability for the next coming days is entirely based on clinical judgement by intensivists and therefore too inaccurate. For this reason, predictive models have much potential for improving planning for ICU patient admission. Our goal is to develop and optimize models for patient survival and ICU length of stay (LOS) based on monitored ICU patient data. Furthermore, these models are compared on their use of sequential organ failure (SOFA) scores as well as underlying raw data as input features. Different machine learning techniques are trained, using a 14,480 patient dataset, both on SOFA scores as well as their underlying raw data values from the first five days after admission, in order to predict (i) the patient LOS, and (ii) the patient mortality. Furthermore, to help physicians in assessing the prediction credibility, a probabilistic model is tailored to the output of our best-performing model, assigning a belief to each patient status prediction. A two-by-two grid is built, using the classification outputs of the mortality and prolonged stay predictors to improve the patient LOS regression models. For predicting patient mortality and a prolonged stay, the best performing model is a support vector machine (SVM) with GA,D=65.9% (area under the curve (AUC) of 0.77) and GS,L=73.2% (AUC of 0.82). In terms of LOS regression, the best performing model is support vector regression, achieving a mean absolute error of 1.79 days and a median absolute error of 1.22 days for those patients surviving a nonprolonged stay. Using a classification grid based on the predicted patient mortality and prolonged stay, allows more accurate modeling of the patient LOS. The detailed models allow to support the decisions made by physicians in an ICU setting.

Multi-scale symbolic entropy analysis provides prognostic prediction in patients receiving extracorporeal life support.

IntroductionExtracorporeal life support (ECLS) can temporarily support cardiopulmonary function, and is occasionally used in resuscitation. Multi-scale entropy (MSE) derived from heart rate variability (HRV) is a powerful tool in outcome prediction of patients with cardiovascular diseases. Multi-scale symbolic entropy analysis (MSsE), a new method derived from MSE, mitigates the effect of arrhythmia on analysis. The objective is to evaluate the prognostic value of MSsE in patients receiving ECLS. The primary outcome is death or urgent transplantation during the index admission.MethodsFifty-seven patients receiving ECLS less than 24 hours and 23 control subjects were enrolled. Digital 24-hour Holter electrocardiograms were recorded and three MSsE parameters (slope 5, Area 6–20, Area 6–40) associated with the multiscale correlation and complexity of heart beat fluctuation were calculated.ResultsPatients receiving ECLS had significantly lower value of slope 5, area 6 to 20, and area 6 to 40 than control subjects. During the follow-up period, 29 patients met primary outcome. Age, slope 5, Area 6 to 20, Area 6 to 40, acute physiology and chronic health evaluation II score, multiple organ dysfunction score (MODS), logistic organ dysfunction score (LODS), and myocardial infarction history were significantly associated with primary outcome. Slope 5 showed the greatest discriminatory power. In a net reclassification improvement model, slope 5 significantly improved the predictive power of LODS; Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in MODS. In an integrated discrimination improvement model, slope 5 added significantly to the prediction power of each clinical parameter. Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in sequential organ failure assessment.ConclusionsMSsE provides additional prognostic information in patients receiving ECLS.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0548-3) contains supplementary material, which is available to authorized users.

S136 An observational cohort study to determine the safety, efficacy and outcome of the early initiation of pressure support ventilation during mechanical ventilation

IntroductionIdentifying the earliest time for initiation of weaning from mechanical ventilation (MV) is important. Weaning trials and guidelines apply screening criteria which have not been validated and which may actually...

Second infections independently increase mortality in hospitalized patients With cirrhosis: the north american consortium for the study of end-stage liver disease (NACSELD) experience

Bacterial infections are an important cause of mortality in cirrhosis, but there is a paucity of multicenter studies. The aim was to define factors predisposing to infection-related mortality in hospitalized patients with cirrhosis. A prospective, cohort study of patients with cirrhosis with infections was performed at eight North American tertiary-care hepatology centers. Data were collected on admission vitals, disease severity (model for endstage liver disease [MELD] and sequential organ failure [SOFA] scores), first infection site, type (community-acquired, healthcare-associated [HCA] or nosocomial), and second infection occurrence during hospitalization. The outcome was mortality within 30 days. A multivariate logistic regression model predicting mortality was created. 207 patients (55 years, 60% men, MELD 20) were included. Most first infections were HCA (71%), then nosocomial (15%) and community-acquired (14%). Urinary tract infections (52%), spontaneous bacterial peritonitis (SBP, 23%) and spontaneous bacteremia (21%) formed the majority of the first infections. Second infections were seen in 50 (24%) patients and were largely preventable: respiratory, including aspiration (28%), urinary, including catheter-related (26%), fungal (14%), and Clostridium difficile (12%) infections. Forty-nine patients (23.6%) who died within 30 days had higher admission MELD (25 versus 18, P < 0.0001), lower serum albumin (2.4 g/dL versus 2.8 g/dL, P = 0.002), and second infections (49% versus 16%, P < 0.0001) but equivalent SOFA scores (9.2 versus 9.9, P = 0.86). The case fatality rate was highest for C. difficile (40%), respiratory (37.5%), and spontaneous bacteremia (37%), and lowest for SBP (17%) and urinary infections (15%). The model for mortality included admission MELD (odds ratio [OR]: 1.12), heart rate (OR: 1.03) albumin (OR: 0.5), and second infection (OR: 4.42) as significant variables. Potentially preventable second infections are predictors of mortality independent of liver disease severity in this multicenter cirrhosis cohort.

Does lactate measurement performed on admission predict clinical outcome on the intensive care unit? A concise systematic review

There is a need for practical, efficient and effective prognostic markers for patients admitted to the intensive care unit (ICU) with sepsis, to identify patients at highest risk and guide and monitor treatment. Although many biomarkers and scoring systems have been advocated, none have yet achieved this elusive combination. Most ICUs already use blood lactate concentrations to monitor patients but the evidence base for this application is unclear. A systematic review of the last five years of evidence of effectiveness of lactate measurement in prediction of outcome in ICUs was performed. It was found that there is a lack of high-quality evidence, and no specific studies of prognostic accuracy. D- or L-Lactate concentrations measured in plasma, serum, whole blood or colonic washings were raised at admission in almost all patient groups, and were higher in patient groups who had the worst outcomes (in-hospital mortality, sequential organ failure). However, there was significant overlap in individual concentrations measured in those who died within 28 days of admission, or who developed multiple organ failure, and those who did not. For serum L-lactate concentrations, no specific cut-off value capable of predicting in-hospital mortality or sequential organ failure could be recommended. The evidence reviewed suggested that whole blood, plasma or serum lactate measurement could not provide specific prognostic information for individual patients. There may be a role for monitoring for normalization of serum D- or L-lactate concentrations during goal-directed therapy in the ICU but further good-quality studies are needed. Measurement of the D-lactate stereoisomer shows promise, such that further studies are warranted.

Rapidly progressive fatal interstitial lung disease in a patient with systemic sclerosis

A 36-year-old woman developed new-onset Raynaud phenomenon and rapidly progressive dyspnea over a 2-week period. A lung biopsy demonstrated pauci-inflammatory nonspecific pneumonitis, which proved refractory to systemic corticosteroid and intravenous cyclophosphamide therapy. Her preterminal course in an intensive care unit was typified by sequential organ failure. Postmortem examination showed extensive organ fibrosis, including severe diffuse alveolar damage and parenchymal fibrosis, and a notable lack of potentially treatable tissue inflammation. Chest radiography, physical examination, screening for autoantibodies, measurement of serum creatinine, creatine phosphokinase, and brain natriuretic peptide levels, cardiac examination, pulmonary function tests, electrocardiography, transthoracic Doppler echocardiography, right heart catheterization, high-resolution thoracic CT, pulmonary ventilation/perfusion scan, lung biopsy. Interstitial lung disease associated with diffuse systemic sclerosis. Treatment with oxygen, oral and intravenous corticosteroids, mycophenolate mofetil and intravenous cyclophosphamide.

High-Frequency Oscillatory Ventilation for Adult Patients With ARDS

High-frequency oscillatory ventilation (HFOV) is characterized by the rapid delivery of small tidal volumes (Vts) of gas and the application of high mean airway pressures (mPaws). These characteristics make HFOV conceptually attractive as an ideal lung-protective ventilatory mode for the management of ARDS, as the high mPaws prevent cyclical derecruitment of the lung and the small Vts limit alveolar overdistension. In this review, we will summarize the literature describing the use of HFOV in adult patients with ARDS. In addition, we will discuss recent experimental studies of HFOV that have advanced our understanding of its mechanical properties. We identified 2 randomized controlled trials (RCTs) and 12 case series evaluating HFOV in adults with ARDS. In these studies, HFOV appears to be safe and consistently improves oxygenation when used as a rescue mode of ventilation in patients with severe ARDS. The two RCTs comparing HFOV to conventional ventilation revealed encouraging results but failed to show a mortality benefit of HFOV over conventional ventilation. Further research is needed to identify optimal patient selection, technique, the actual Vt delivered, and the role of combining HFOV with other interventions, such as recruitment maneuvers, prone positioning, and nitric oxide.

Long-term survival, quality of life, and quality-adjusted life-years among critically ill elderly patients*

To assess mortality, quality of life (QOL), and quality-adjusted life-years (QALYs) for critically ill elderly patients. Cross-sectional survey. A ten-bed medical-surgical intensive care unit (ICU) in a tertiary care university hospital. The study group included 882 elderly patients (> or =65 yrs of age) and 1,827 controls (<65 yrs of age) treated during the period of 1995 to 2000. None. Mortality was assessed during the ICU and hospital stays, and 12, 24, and 36 months after ICU discharge. The cumulative 3-yr mortality rate among the elderly (57%) was higher (p < .05) than that among the controls (40%). The majority (66%) of the elderly nonsurvivors died within 1 month after intensive care discharge. All elderly patients with day-1 Sequential Organ Failure (SOFA) scores >15 died during the ICU stay. QOL was assessed with EQ-5D and RAND-36 measures from 10 months to 7 yrs after discharge. The majority (88%) of the elderly survivors assessed their present health state as good or satisfactory; 66% found it to be similar or better than 12 months earlier, and 48% similar or better than their preadmission state. QOL measures by RAND-36 revealed that aging decreased their competencies most in physical functioning, physical role limitations, and vitality, but the elderly had better values in mental health than the controls. However, QALYs of the elderly respondents were 21% to 35% lower than the mean QALY minus 2 sd units of the age- and gender-adjusted general population. High age alone is not a valid reason to refuse intensive care, but the benefits perceived by intensive care seem to decrease with aging, if reflected as QALYs. However, 97% of the elderly survivors lived at home and 88% of them considered their QOL satisfactory or good after hospital discharge. Therefore, more reliable information on the outcome for the elderly is clearly needed.

Usefulness of an Estimation of Physiologic Ability and Surgical Stress (E‐PASS) Scoring System to Predict the Incidence of Postoperative Complications in Gastrointestinal Surgery

Surgical intervention induces various host responses to maintain homeostasis. When postoperative inflammation is intense and persists for a long time, postoperative complications may occur, sometimes developing into multiple organ failure. Therefore, it is very important to assess surgical stress and predict the risk of morbidity and mortality. Using a new scoring system, an estimation of physiologic ability and surgical stress (E-PASS) scoring system, surgical stress following gastrointestinal surgery was evaluated to assess the feasibility of this scoring system. This system comprises a preoperative risk score (PRS), a surgical stress score (SSS), and a comprehensive risk score (CRS) that is calculated from both the PRS and the SSS. The relationship of the E-PASS score to the incidence of morbidity and mortality was examined. The relationship between the E-PASS score and a sequential organ failure (SOFA) score was also evaluated. The CRS had a significant positive correlation between not only the incidence but also the grade of postoperative complications. Total maximum SOFA score in patients with a CRS of more than 1 was significantly higher than that in patients with a CRS of less than 1. In conclusion, the E-PASS scoring system will be useful for predicting and recognizing the risk of postoperative complications. This scoring system is brief, simple, and reproducible and can be useful in all types of hospitals.

Heart rate variability in emergency department patients with sepsis.

To test the hypothesis that heart rate variability (HRV) can provide an early indication of illness severity among patients presenting to the emergency department (ED) with sepsis. The authors enrolled a convenience sample of 15 ED patients meeting the American College of Chest Physicians/Society of Critical Care Medicine criteria for sepsis. Each patient had continuous Holter monitoring performed in the ED. Acute Physiology and Chronic Health II (APACHE II) and Sequential Organ Failure (SOFA) scores were calculated for the day of presentation. Holter tapes obtained in the ED were analyzed off-line to calculate HRV variables for the 5-minute segment with the least artifact and non-sinus beats. These variables were correlated with APACHE II and SOFA scores. LFnu (normalized low-frequency power), an assessment of the relative sympathetic contribution to overall HRV, was correlated with increased illness severity as calculated using APACHE II (r = -0.67, r(2) = 0.43) and SOFA (r = -0.80, r(2) = 0.64) scores. LF/HF ratio (low-frequency/high-frequency ratio), a measure of sympathovagal balance, was correlated with the SOFA score [r = -0.54 (95% CI = -0.83 to -0.01), r(2) = 0.29]. All five patients who required critical care monitoring or ventilatory support or who died during the first 5 days of their hospitalization had LFnu values below 0.5 and LF/HF ratios less than 1.0. None of the patients with measurements greater than these threshold values died or required these interventions during the five days following admission. A single variable, LFnu, which reflects sympathetic modulation of heart rate, accounted for 40-60% of the variance in illness severity scores among patients presenting to the ED with sepsis. HRV, as reflected in LFnu and the LF/HF ratio and measured with a single brief (5-minute) period of monitoring while in the ED, may provide the emergency physician with a readily available, noninvasive, early marker of illness severity. The threshold effect of LFnu and LF/HF in the prediction of early clinical deterioration was an unexpected finding and should be regarded as hypothesis-generating, pending further study.

Heart Rate Variability in Emergency Department Patients with Sepsis

Abstract Objective: To test the hypothesis that heart rate variability (HRV) can provide an early indication of illness severity among patients presenting to the emergency department (ED) with sepsis. Methods: The authors enrolled a convenience sample of 15 ED patients meeting the American College of Chest Physicians/Society of Critical Care Medicine criteria for sepsis. Each patient had continuous Holter monitoring performed in the ED. Acute Physiology and Chronic Health II (APACHE II) and Sequential Organ Failure (SOFA) scores were calculated for the day of presentation. Holter tapes obtained in the ED were analyzed off‐line to calculate HRV variables for the 5‐minute segment with the least artifact and non‐sinus beats. These variables were correlated with APACHE II and SOFA scores. Results: LFnu (normalized low‐frequency power), an assessment of the relative sympathetic contribution to overall HRV, was correlated with increased illness severity as calculated using APACHE II (r = ‐0.67, r2= 0.43) and SOFA (r = ‐0.80, r2= 0.64) scores. LF/HF ratio (low‐frequency/high‐frequency ratio), a measure of sympathovagal balance, was correlated with the SOFA score [r = ‐0.54 (95% CI = ‐0.83 to ‐0.01), r2= 0.29]. All five patients who required critical care monitoring or ventilatory support or who died during the first 5 days of their hospitalization had LFnu values below 0.5 and LF/HF ratios less than 1.0. None of the patients with measurements greater than these threshold values died or required these interventions during the five days following admission. Conclusions: A single variable, LFnu, which reflects sympathetic modulation of heart rate, accounted for 40‐60% of the variance in illness severity scores among patients presenting to the ED with sepsis. HRV, as reflected in LFnu and the LF/HF ratio and measured with a single brief (5‐minute) period of monitoring while in the ED, may provide the emergency physician with a readily available, noninvasive, early marker of illness severity. The threshold effect of LFnu and LF/HF in the prediction of early clinical deterioration was an unexpected finding and should be regarded as hypothesis‐generating, pending further study.

Dietary prevention of experimental shock lesions.

A MAJOR difficulty in the interpretation of experiments in shock is the variation of response from one animal species to another. In particular, the terminal mechanisms which lead to death appear to differ when one compares the human with the intact laboratory animal. There is no doubt as to the universal dependence of vertebrates upon the delivery of oxygen and metabolic substrates to the membranes of the individual cells via the circulation of the blood. There is no doubt that a prolonged deficiency of capillary circulation results in reversion to an anaerobic metabolic state and a gradual loss of tissue viability. It is in the course of this progression toward sequential organ failure that the major species differences between the dog, the rat, and man became more clearly demarcated. Dogs submitted to the usual hemorrhagic shock procedures by the techniques of Fine or Wiggers are brought to a standard stage