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Risk Stratification of the Potentially Septic Patient in the Emergency Department: The Mortality in the Emergency Department Sepsis (MEDS) Score
The Journal of Emergency Medicine, Vol. 37, No. 3, pp. 319 –327, 2009 Copyright © 2009 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/09 $–see front matter
doi:10.1016/j.jemermed.2009.03.016
Evidence-Based Medicine
RISK STRATIFICATION OF THE POTENTIALLY SEPTIC PATIENT IN THE EMERGENCY DEPARTMENT: THE MORTALITY IN THE EMERGENCY DEPARTMENT SEPSIS (MEDS) SCORE Christopher R. Carpenter, MD, MSC,* Samuel M. Keim, MD, MS,† Suneel Upadhye, MD, MSC,‡ H. Bryant Nguyen, MD, MS,§ and Best Evidence in Emergency Medicine Investigator Group㛳 *Washington University School of Medicine in St. Louis, St. Louis, Missouri, †Department of Emergency Medicine, The University of Arizona College of Medicine, Tucson, Arizona, ‡Division of Emergency Medicine, McMaster University, Hamilton, Ontario, Canada, §Department of Emergency Medicine, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Loma Linda University, Loma Linda, California, and 㛳Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada Reprint Address: Samuel M. Keim, MD, MS, Department of Emergency Medicine, The University of Arizona College of Medicine, PO Box 245057, Tucson, AZ 85724-5057
e Abstract—Background: The prompt recognition and management of septic patients remains a challenge within the busy Emergency Department (ED). Prognostic screening aids have traditionally required time-delayed laboratory measurements not validated upon the emergency medicine population. Recently, a brief prognostic tool has been derived and subsequently validated in heterogeneous ED populations. Clinical Question: Can a risk-stratification tool predict 1-month mortality in ED patients with suspected infection? Evidence Review: Six studies evaluating the Mortality in the Emergency Department Sepsis (MEDS) score were identified and evaluated. Results: Higher MEDS scores are associated with increasing mortality. MEDS score’s short- and long-term prognostic accuracy is superior to other sepsis scales as well as isolated biomarkers C-reactive protein and procalcitonin. MEDS’ prognostic accuracy in severe sepsis is inferior to undifferentiated systemic inflammatory response syndrome (SIRS) patients. Conclusion: The MEDS score is an accurate and reliable prognostic tool for 28-day mortality in ED SIRS patients, but may not be optimal for those with severe sepsis. © 2009 Elsevier Inc.
CASE A 67-year-old-woman presents to the Emergency Department (ED) with complaints of fever, cough, and weakness for the last 2 days. She reports no past medical history and lives at home. She denies any recent travel, hospitalization, or exposures to possible health careacquired pneumonia. Physical examination reveals temperature 38.3°C, heart rate 110 beats/min, blood pressure 125/50 mm Hg, respiratory rate 22 breaths/min, and a normal mental status examination. Her chest radiograph reveals a left lower lobe infiltrate, and white blood cell count is 14,000 per mm3 with 12% bands and 150,000 per mm3 platelets. Blood cultures are sent, appropriate antimicrobial management initiated, and the emergency physician contemplates what her prognosis is and whether any systemic inflammatory response syndrome (SIRS)-related risk-stratification tools have yet been validated. CLINICAL QUESTION Can a risk-stratification tool predict 1-month mortality in ED patients with suspected infection?
e Keywords— evidence-based medicine; clinical decision rules; sepsis
RECEIVED: 26 February 2009; ACCEPTED: 24 March 2009 319
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CONTEXT In the United States, over 700,000 patients present to the ED each year with sepsis, severe sepsis, or septic shock (1). Approximately 40% of sepsis patients initially present to the ED, and intensive care unit (ICU) admission is frequently delayed (1,2). Although early goal-directed therapy significantly reduces sepsis-related mortality, non-specific presentations in overcrowded EDs may result in poor disease recognition and suboptimal care (3–5). Multiple scoring systems have been derived to quantify disease severity in critically ill patients (6 –13). Unfortunately, these risk-stratification aids require parameters not readily available in the first hours of a patient’s presentation. Furthermore, they are complicated to administer and have not been validated in ED populations. In addition, experienced critical care physician gestalt has outperformed many of these screening tools (14). An ED-validated, reliable sepsis mortality screening tool would be beneficial for several reasons. Recognition of high-risk SIRS patients could facilitate focused resource allocation upon those most likely to benefit. Some components of aggressive sepsis management, such as recombinant human activated protein C, have life-threatening side effects and should be used on only the most critically ill subset most likely to benefit (15–17). Additionally, a universal stratification instrument could enhance communication between the ED and the ICU, optimizing a seamless transition of care in chaotic environments. Finally, subsequent sepsis research can stratify findings between higher and lower risk subsets in reporting diagnostic and therapeutic findings, thereby permitting physicians to more effectively apply results to their own populations (Figure 1). EVIDENCE SEARCH Using the TRIP (Translating Research into Practice) database (http://www.tripdatabase.com), the search term “emergency department sepsis score” was entered on December 12, 2008 and identified a secondary review of the validation of the Mortality in the Emergency Department Sepsis (MEDS) score on PUBMED. On PUBMED, the “related articles” tab was selected, yielding 114 citations. Among these results, six were chosen for this critical appraisal. EVIDENCE REVIEW MEDS Derivation Mortality in Emergency Department Sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Critical Care Medicine, 2003 (18).
Population. All adults over age 18 years presenting to Beth Israel Deaconess Medical Center ED (Boston, MA) with suspected infection (as judged by an obtained blood culture) were eligible. In total, 3179 patient encounters were obtained, with 2070 in the derivation cohort and 1109 in the validation cohort. The mean age was 61 years; about 46% of the subjects were men. Study design. From February 2000 through February 2001, ED charts of all patients were reviewed by trained reviewers unaware of the patient’s hospital course on either the day of admission or the next day. No other chart review methods are provided (19,20). Using a modified version of a co-morbid diseaserelated prognosis method to identify subjects with ⬎ 50% likelihood of 30-day mortality, the investigators included “terminal illness” as one candidate variable. SIRS was defined by two or more of the findings in Table 1 (21,22). Severe sepsis was defined as SIRS with organ dysfunction, and septic shock was severe sepsis with fluid-refractory hypotension. Suspected infection was abstracted from the medical decisionmaking portion of the physician documentation and was limited to suspected lower respiratory tract infection, urinary tract infection, intra-abdominal infection, skin or soft tissue infection, and endocarditis. Patients were randomized into a derivation set (two-thirds of cohort) and a validation set (one-third of cohort). Using a logistic regression model, variables associated with the primary outcome were analyzed for independent association with 28-day mortality. Statistical validation of the model was undertaken using the bootstrap method before the model’s prognostic test performance on the validation cohort was evaluated. Finally, investigators analyzed the MEDS score prognostic test performance on the subset of patients more likely to receive aggressive resuscitation by excluding those with fatal disease, dementia, or nursing home residence. Primary outcome. The primary outcome was 28-day hospital mortality. Exclusion criteria. Patients were not eligible if they were under age 18 years or did not have a blood culture obtained in the ED or within 3 h of floor arrival. Main results. In-hospital mortality occurred within 28 days in 110 derivation set patients (5.3%) and 63 validation set patients (5.7% mortality rate). From the 24 variables associated with in-hospital mortality, nine variables were independently associated with the outcome and were used to develop the MEDS score (Table 2). The receiver operating characteristic (ROC)
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EBM – Prognosis Searching for, appraising and applying the best evidence available to assist clinical decisions regarding prognosis and risk assessment. The Prospective Cohort study design produces the highest quality data for analysis in derivation and validation of prognosis estimates. These estimates frequently are presented as outcome scores. Search with a disease keyword with PubMed Clinical Queries search with the “Prognosis” option or the term “prognosis” or “follow up studies.” TRIP Database Medical search engine with emphasis on evidence-based medicine (EBM) and clinical guidelines and queries, including content from Cochrane and Bandolier: www.tripdatabase.com. Logistic Regression A statistical technique that builds a prediction model of an individual’s dichotomous outcome status, for example, mortality, from variables that can be either numerical or categorical. For example, a septic patient’s estimated probability of death in 30 days is found to be associated with age, presence of altered mental status and shock. Kappa A measure of the degree of agreement between observers of a single event adjusted for chance alone. Receiver Operating Characteristic (ROC) Curve A figure that depicts the power of a diagnostic test compared to a reference (gold) standard. The figure typically plots sensitivity (true positive rate) on the vertical axis against 1 – specificity (false positive rate) for different cut-off points for the diagnostic test. The area under the curve (AUC) for a perfect diagnostic test would be 1.0 and 0.5 for one that is no better than chance. Figure 1. Evidence-based medicine teaching points.
area under the curve (AUC) for the derivation set was 0.82, and 0.76 in the validation set. In the validation set, mortality increased with higher MEDS scores, with a range from 1.1% to 39% at the low and high end, respectively. The MEDS score performed equally well in those likely to receive more aggressive care with AUC 0.80.
MEDS Validation Risk stratification of severe sepsis patients in the emergency department. Emergency Medicine Journal, 2006 (23).
investigators included only subjects with severe sepsis as defined by sepsis-related organ dysfunction requiring immediate ICU admission: hypotension, altered sensorium, acute oliguria, or arterial metabolic acidosis. MEDS scores for each patient were then retrospectively calculated and subjects were stratified into high-risk (MEDS 12–27) or low-risk (MEDS ⬍ 12) subsets. Primary outcome. The primary outcome was 28-day hospital mortality rate, although the investigators also evaluated total hospital length of stay and compared the MEDS score ROC curve to the Acute Physiology and Chronic Health Evaluation (APACHE) II score ROC curve (6).
Population. Adult patients admitted from the Shin Kong Wu Ho-Su Memorial Hospital ED (Taipei, Taiwan) to the ICU with severe sepsis were eligible. From 1696 patients admitted to non-surgical ICUs, 276 met inclusion criteria, with mean age 72 years and 45% men.
Exclusion criteria. Patients were not eligible if they were under age 18 years, pregnant, dead on arrival to the ED, suffered multiple trauma before ICU admission, underwent major surgery before ICU admission, or had preexisting do-not-attempt-resuscitation orders documented by treating emergency physicians.
Study design. This was a retrospective non-interventional cohort study between January 2002 and December 2003. Eligible patients were identified from a central electronic database with data abstraction performed by one of two physicians “with extensive experience in chart review procedures” using a standard data collection checklist. The
Main results. Patients were evenly divided between the low-risk (51.8%) and the high-risk (48.2%) groups, but patients with MEDS score ⱖ 12 had significantly higher 28-day mortality (48.9% vs. 17.5%, p ⬍ 0.01). Additionally, the MEDS score had a significantly better discriminatory performance than the APACHE II score (ROC
322 Table 1. Systemic Inflammatory Response Syndrome (SIRS) SIRS is defined as the presence of two or more of the following: Heart rate ⬎ 90 beats/min Respiratory rate ⬎ 20 breaths/min or oxygen saturation ⬍ 90% or need for ⬎ 0.4 FIO2 to maintain saturation Temperature ⬎ 38°C or ⬍ 35.5°C White blood cell count ⬎ 15,000 cells/mm3 or bands ⬎ 10%
area 0.75 vs. 0.26, p ⬍ 0.01). The MEDS score was not associated with hospital length of stay. Performance of severity of illness scoring systems in emergency department patients with infection. Academic Emergency Medicine, 2007 (24). Population. Consecutive adult patients with suspected infection presenting to the Beth Israel Deaconess Medical Center ED (Boston, MA) were eligible. A total of 2132 unique patients were recruited during the study interval, with mean age 61 years and 76% Caucasian. Study design. This was a secondary analysis of a prospective observational cohort between December 2003 and September 2004. Eligible patients were identified via daily review of ED census logs with data collection abstracted thereafter by trained research assistants blinded to the outcome data. Presence of infection was ascertained by analyzing the physicians’ medical decision-making documentation. In calculating the scores, absent or missing data were treated as normal. Investigators computed scores for MEDS, the Confusion Urea Nitrogen Respiratory Rate Blood Pressure 65 Years or Older (CURB65) and the Rapid Emergency Medicine Score (REMS) (25,26). The latter two instruments had been derived for pneumonia and non-surgical ED patients, respectively. Neither had been validated on general ED patients with suspected infections. The REMS was modified (mREMS) because not every subject had a detailed Glasgow Coma Scale score reported.
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Performance of the mortality in emergency department sepsis score for predicting hospital mortality among patients with severe sepsis and septic shock. American Journal of Emergency Medicine, 2008 (27). Population. Subjects were enrolled from Carolinas Medical Center ED (Charlotte, NC) if over age 17 years with suspected or confirmed infection, two or more SIRS criteria, and systolic blood pressure ⬍ 90 mm Hg or mean arterial pressure ⬍ 65 mm Hg after an isotonic fluid bolus or anticipated need for ICU care with lactate ⱖ 4 mmol/L. In total, 143 patients were enrolled, with mean age 58 years, but little other demographic information is provided by which to judge the external validity of this population. Study design. This was a pre-planned secondary analysis of prospectively recruited patients in an early goal-directed therapy (EGDT) trial from August 2004 through November 2006. MEDS score variables were collected prospectively, but scores were not calculated during the clinical encounter. Whether outcome assessors were blinded to the MEDS score is unclear. The investigators also do not clearly state who determined the primary outcome or when it was determined. Primary outcome. The primary outcome was in-hospital mortality. Exclusion criteria. Subjects were excluded if they were under age 17 years, required immediate surgery, or had an absolute contraindication for a chest central venous catheter. Main results. In-hospital mortality occurred in 23%, including 27% pre-EGDT and 18% post-EGDT. The average MEDS score was 10 points. The MEDS score performed poorly overall (AUC 0.61; 95% CI 0.50 – 0.72) and in both the pre-EGDT (AUC 0.69; 95% CI 0.56 – 0.82) and the post-EGDT (AUC 0.53; 95% CI
Primary outcome. The primary outcome was 28-day mortality. Exclusion criteria. None reported.
Table 2. Mortality in Emergency Department Sepsis Score (MEDS) Points
Main results. Eight-three patients died (3.9%; 95% confidence interval [CI] 3.1– 4.7%). As each score increased by one point, so did the odds of death: MEDS 1.4, CURB-65 2.4, mREMS 1.4. Although widely overlapping, MEDS had superior prognostic test performance (AUC 0.85; 95% CI 0.81– 0.89) compared with CURB-65 (AUC 0.79; 95% CI 0.74 – 0.83) or mREMS (AUC 0.80; 95% CI 0.75– 0.85).
Rapidly terminal co-morbid illness Age ⬎ 65 years Bands ⬎ 5% Tachypnea or hypoxemia Shock Platelet count ⬍ 150,000 mm3 Altered mental status Nursing home resident Lower respiratory infection
6 3 3 3 3 3 2 2 2
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0.33– 0.74) subsets. In the moderate-risk groups (MEDS score 5–15), the MEDS score consistently underestimated patient mortality by 14%. Prognostic value of mortality in emergency department sepsis score, procalcitonin, and C-reactive protein in patients with sepsis at the emergency department. Shock, 2008 (28). Population. Consecutive ED patients at Taiwan University Hospital (Taipei, Taiwan) who fulfilled the SIRS criteria with a presumed infectious etiology were eligible. A total of 525 patients were recruited, with a median age of 64 years. Study design. The ED charts of all SIRS patients were reviewed on the day of admission or the next day by one investigator. The authors do not elaborate upon any chart review methods, but they did confirm any missing co-variate via telephone or personal interview (19,20). Terminal illness was defined using the same criteria as Shapiro (18,21). In addition to the clinical data necessary to calculate the MEDS score, investigators also collected blood samples for C-reactive protein (CRP) and procalcitonin (PCT) within 2 h of ED admission to assess the prognostic test characteristics of these inflammatory biomarkers for the sepsisrelated mortality outcomes. Primary outcome. The primary outcome was early (5 day) or late (6 –30 day) all-cause mortality. Exclusion criteria. Subjects were excluded if younger than 15 years, missing data or lost to follow-up, preexisting thyroid disease, or non-infectious etiology of SIRS identified. Main results. After exclusion of 66 subjects left 525 for analysis, the all-cause 30-day mortality rate was 10.5%. Sepsis severity in this cohort was 76% sepsis, 19.4% severe sepsis, and 4.6% septic shock with corresponding mortality 4.3%, 27.5%, and 41.7%, respectively. An elevated CRP (⬎ 60 mg/L) was noted in 41.9% of subjects, and an elevated PCT (⬎ 0.5 ng/mL) was noted in 30.9%. For short-term mortality, the MEDS score had superior prognostic accuracy (c-statistic 0.89) than PCT (0.76) or CRP (0.68). The MEDS score also more accurately identified those at risk for late mortality with C-statistic 0.78 as opposed to PCT 0.70 and CRP 0.63. However, the investigators note that the MEDS score is more specific, but less sensitive than PCT for both early and late mortality, suggesting a complementary role for PCT in screening patients for sepsis-related mortality, with the MEDS score better modeled to confirm high-
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risk suspicions upon the PCT-positive subset. The investigators did not test this hypothesis, however. Validation of the Mortality in Emergency Department Sepsis (MEDS) score in patients with the systemic inflammatory response syndrome (SIRS). Critical Care Medicine, 2008 (29). Population. ED patients at four university hospitals: University of Colorado Hospital, Denver Health Medical Center, Albert Einstein Medical Center, and the University of Pennsylvania. All adult patients meeting SIRS criteria (Table 1) and admitted to the hospital were eligible (22). A total 385 patients were enrolled, with 55% men and median age 56 years. The median hospital length of stay was 5 days, and 11% required mechanical ventilation. Study design. This was a prospective convenience sampling over a 6-month period. Data collection was performed by research assistants or clinical physicians using a uniform closed response instrument. The primary outcome was ascertained by a hospital record review from the index admission without explicit methods or telephone follow-up for discharged patients (19). At one institution, an investigator blinded to the MEDS score abstracted the variables from the medical records to assess the reliability of the prospectively computed score. Investigators used a post hoc logistic regression analysis using the summed MEDS score for each patient as the independent variable and 28-day mortality as the dependent variable to recalibrate a revised MEDS score. Primary outcome. The primary outcome was 28-day allcause mortality. Exclusion criteria. Subjects were excluded if they presented as the result of trauma, were previously enrolled, were a direct admission or transfer from another hospital, or if they were not enrolled within 2 h of ED presentation. The investigators do not provide any details about number of or reasons for exclusions. Main results. Among 385 enrolled patients, 33 (9%; 95% CI 6 –12%) died. The ED diagnosis was available for only 225 (58%) and, of these, 165 (73%) had a source of infection, including 6 (4%) who met the criteria for severe sepsis. In the entire cohort, 184 (48%) were very low, 82 (21%) were low, 82 (21%) moderate, 23 (6%) high, and 9 (2%) very high MEDS mortality scores. The mortality rates associated with the MEDS score were similar to Shapiro’s derivation figures ranging from 0.6% to 40% and increasing progressively. The AUC for
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MEDS (0.88; 95% CI 0.83– 0.92) was superior to the modified MEDS (0.84; 95% CI 0.78 – 0.89) and lactate (0.78; 95% CI 0.66 – 0.90). Terminal illness had moderate reliability ( ⫽ 0.64), but all other MEDS variables had excellent inter-rater reproducibility ( range 0.82– 1.00). Overall, the MEDS score correlation was 0.93 (0.86 – 0.97).
CONCLUSION After validation across prospective samples from multiple institutions, the MEDS score is an accurate and reliable risk-stratification tool for 28-day mortality in ED patients with SIRS. The MEDS score is a Level II clinical decision rule and can therefore be used in various settings with confidence. Some elements of the MEDS score may prove problematic due to interpretation bias (terminal illness) or lack of routine availability (band counts in an era of automated white blood cell counts). Additionally, future inclusion of lactate or other evolving biomarkers may augment the prognostic performance of the MEDS score. The MEDS score lacked prognostic accuracy in the severe sepsis patients, but these are probably not the subset most likely to benefit from the tool because most of these patients will be admitted to the ICU regardless of their score. One recent retrospective application of the APACHE II, Simplified Acute Physiology Score, Mortality Prediction Model, and MEDS suggested that MEDS had the least discriminatory ability in identifying high-risk ED sepsis patients (6,9,30,31). Nonetheless, the MEDS score is currently the superior tool for ED risk-stratification of potentially septic patients and is also associated with long-term mortality (32).
COMMENTARY BY H. BRYANT NGUYEN, MD, MS At the turn of this century, we have now witnessed significant progress in our understanding of the pathogenesis, recognition, and management of sepsis (33,34). As emergency physicians, we have moved beyond simply considering a patient with infection on vasopressors and mechanical ventilation as merely septic. It is crucial that emergency physicians understand the definitions of severe sepsis and septic shock, as early intervention in the ED for this subgroup has been shown to significantly impact outcome. A quandary remains, however, for the bedside clinician in how to best identify and estimate prognosis in these high-risk patients to appropriately intervene. Often, we are presented with a patient similar to our case
scenario. After administering the usual antibiotic and fluid bolus, we are faced with a difficult disposition decision in an elderly patient with a fever, slight bandemia, and suspected bacteremia. The availability of a prognosis prediction tool such as the MEDS score seems prudent. Our patient would have a calculated MEDS score of 11 and a predicted mortality of approximately 9% (Table 3), suggesting that she may require inpatient care. In this case, MEDS seems to be a useful mortality predictor for patients presenting to the ED with suspected sepsis. The score was examined in multiple patient populations and was shown to be accurate in predicting patient mortality. Although MEDS has increased our awareness for sepsis patients in the ED, we need to recognize the limitations in the patient population that comprised the derivation set. The score was originally derived from an ED patient population with a suspected infection as defined by a clinician obtaining a blood culture. The overall mortality for this sample size was a modest 5.3%. This is much lower than the commonly cited 18% mortality for sepsis (1). MEDS therefore seems to accurately predict outcome in the low-risk group of patients in whom a clinician is considering an infectious source. This evidence review also highlights the difference between sepsis, severe sepsis, and septic shock. Sepsis is a systemic response to a local infection, resulting in such signs as fever, tachycardia, tachypnea, leukocytosis, or hyperglycemia. This group of patients may best be prognosticated with MEDS. Severe sepsis includes organ dysfunction or hypoperfusion in the presence of infection. Septic shock occurs when a sepsis patient is refractory to fluid resuscitation, requiring vasopressor therapy. A severe sepsis patient with significant hypoperfusion, such as with lactate ⱖ 4 mmol/L, is also considered in shock, as the criteria of hypotension is no longer required (35). MEDS is an outcome prediction tool for those patients in whom we initially suspect sepsis but not necessarily those patients with severe sepsis or septic shock, in whom we would immediately intervene with EGDT. Only 2.5% of patients in the derivation set presented in septic shock. Lactate was not examined
Table 3. MEDS Score Mortality Estimate
Very low risk Low risk Moderate risk High risk Very high risk
MEDS Score Range
28-Day Mortality Rate (%)*
0–4 5–7 8–12 13–15 ⬎ 15
0.4–11 3.3–5.0 6.6–19 16.1–32.0 39.1–40.0
* Mortality estimates derived from the derivation and validation trials summarized in this review. MEDS ⫽ Mortality in Emergency Department Sepsis.
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nor incorporated as a component of the score. The tool’s creators did not intend MEDS to predict outcome or guide the clinical decisions to initiate intensive therapies such as EGDT in the very high-risk patients. As a result, MEDS consistently underestimates the mortality in those patients who would qualify for EGDT (27,31). The application, therefore, of MEDS in ED patients with suspected sepsis will not allow a clinician to fully risk-stratify patients with significant lactic acidosis or multi-organ failure. For example, if our patient had a lactate level ⬎ 4 mmol/L, her mortality would be at least 28%, instead of 9% as predicted by MEDS (36). There is good evidence that normotensive severe sepsis patients with significant lactic acidosis should receive early antibiotics, hemodynamic monitoring and resuscitation targeting optimal central venous pressure, mean arterial pressure, and central venous oxygenation (37,38). An estimated mortality of 9% per MEDS calculation may not produce adequate concern in the clinician, and this patient may suffer unresolved tissue hypoperfusion. With the barriers surrounding the initiation of intensive therapies in the ED such as EGDT and the sepsis bundle, we still await a prediction tool that can assist clinicians to appropriately risk-stratify patients with severe sepsis or septic shock during their golden hours of presentation (39).
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C. R. Carpenter et al. predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005;45:524 – 8. 37. Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004;32:1637– 42. 38. Arnold RC, Shapiro NI, Jones AE, et al. Multi-center study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock 2008 Dec 22 [Epub ahead of print]. 39. Carlbom DJ, Rubenfeld GD. Barriers to implementing protocolbased sepsis resuscitation in the emergency department—results of a national survey. Crit Care Med 2007;35:2525–32.
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ARTICLE SUMMARY 1. Why is this topic important? Estimating short-term mortality in suspected sepsis may facilitate effective allocation of finite critical care resources to a population most likely to benefit. 2. What is the clinical question? Can a risk-stratification tool predict 1-month mortality in emergency department (ED) patients with suspected infection? Search strategy Translating Research into Practice (TRIP) database search using the search term “emergency department sepsis score,” which linked to PUBMED, whereby the related articles tab was used to identify additional findings. Citations Appraised Mortality in emergency department sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Crit Care Med, 2003 (18). Risk stratification of severe sepsis patients in the emergency department. Emerg Med J, 2006 (23). Performance of severity of illness scoring systems in emergency department patients with infection. Acad Emerg Med, 2007 (24). Performance of the mortality in emergency department sepsis score for predicting hospital mortality among patients with severe sepsis and septic shock. Am J Emerg Med, 2008 (27). Prognostic value of mortality in emergency department sepsis (MEDS) score, procalcitonin, and c-reactive protein in patients with sepsis at the emergency department. Shock, 2008 (28). Validation of the mortality in emergency department sepsis (MEDS) score in patients with the systemic inflammatory response syndrome (SIRS). Crit Care Med, 2008 (29). 3. Are the results valid? Yes. MEDS is the only sepsis prognostic screening tool derived and validated in ED populations and has been validated across heterogeneous populations. 4. What are the results? Higher MEDS scores are associated with higher sepsisrelated mortality. MEDS may underestimate mortality in severe sepsis populations. 5. Can I apply the results to my practice? Yes, MEDS is a Level II Clinical Decision Rule. MEDS has not undergone implementation testing to determine if the rapid identification of high-risk subsets will improve patient-important outcomes, clinical efficiency, or cost-effectiveness.
doi:10.1016/j.jemermed.2009.03.016
Evidence-Based Medicine
RISK STRATIFICATION OF THE POTENTIALLY SEPTIC PATIENT IN THE EMERGENCY DEPARTMENT: THE MORTALITY IN THE EMERGENCY DEPARTMENT SEPSIS (MEDS) SCORE Christopher R. Carpenter, MD, MSC,* Samuel M. Keim, MD, MS,† Suneel Upadhye, MD, MSC,‡ H. Bryant Nguyen, MD, MS,§ and Best Evidence in Emergency Medicine Investigator Group㛳 *Washington University School of Medicine in St. Louis, St. Louis, Missouri, †Department of Emergency Medicine, The University of Arizona College of Medicine, Tucson, Arizona, ‡Division of Emergency Medicine, McMaster University, Hamilton, Ontario, Canada, §Department of Emergency Medicine, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Loma Linda University, Loma Linda, California, and 㛳Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada Reprint Address: Samuel M. Keim, MD, MS, Department of Emergency Medicine, The University of Arizona College of Medicine, PO Box 245057, Tucson, AZ 85724-5057
e Abstract—Background: The prompt recognition and management of septic patients remains a challenge within the busy Emergency Department (ED). Prognostic screening aids have traditionally required time-delayed laboratory measurements not validated upon the emergency medicine population. Recently, a brief prognostic tool has been derived and subsequently validated in heterogeneous ED populations. Clinical Question: Can a risk-stratification tool predict 1-month mortality in ED patients with suspected infection? Evidence Review: Six studies evaluating the Mortality in the Emergency Department Sepsis (MEDS) score were identified and evaluated. Results: Higher MEDS scores are associated with increasing mortality. MEDS score’s short- and long-term prognostic accuracy is superior to other sepsis scales as well as isolated biomarkers C-reactive protein and procalcitonin. MEDS’ prognostic accuracy in severe sepsis is inferior to undifferentiated systemic inflammatory response syndrome (SIRS) patients. Conclusion: The MEDS score is an accurate and reliable prognostic tool for 28-day mortality in ED SIRS patients, but may not be optimal for those with severe sepsis. © 2009 Elsevier Inc.
CASE A 67-year-old-woman presents to the Emergency Department (ED) with complaints of fever, cough, and weakness for the last 2 days. She reports no past medical history and lives at home. She denies any recent travel, hospitalization, or exposures to possible health careacquired pneumonia. Physical examination reveals temperature 38.3°C, heart rate 110 beats/min, blood pressure 125/50 mm Hg, respiratory rate 22 breaths/min, and a normal mental status examination. Her chest radiograph reveals a left lower lobe infiltrate, and white blood cell count is 14,000 per mm3 with 12% bands and 150,000 per mm3 platelets. Blood cultures are sent, appropriate antimicrobial management initiated, and the emergency physician contemplates what her prognosis is and whether any systemic inflammatory response syndrome (SIRS)-related risk-stratification tools have yet been validated. CLINICAL QUESTION Can a risk-stratification tool predict 1-month mortality in ED patients with suspected infection?
e Keywords— evidence-based medicine; clinical decision rules; sepsis
RECEIVED: 26 February 2009; ACCEPTED: 24 March 2009 319
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CONTEXT In the United States, over 700,000 patients present to the ED each year with sepsis, severe sepsis, or septic shock (1). Approximately 40% of sepsis patients initially present to the ED, and intensive care unit (ICU) admission is frequently delayed (1,2). Although early goal-directed therapy significantly reduces sepsis-related mortality, non-specific presentations in overcrowded EDs may result in poor disease recognition and suboptimal care (3–5). Multiple scoring systems have been derived to quantify disease severity in critically ill patients (6 –13). Unfortunately, these risk-stratification aids require parameters not readily available in the first hours of a patient’s presentation. Furthermore, they are complicated to administer and have not been validated in ED populations. In addition, experienced critical care physician gestalt has outperformed many of these screening tools (14). An ED-validated, reliable sepsis mortality screening tool would be beneficial for several reasons. Recognition of high-risk SIRS patients could facilitate focused resource allocation upon those most likely to benefit. Some components of aggressive sepsis management, such as recombinant human activated protein C, have life-threatening side effects and should be used on only the most critically ill subset most likely to benefit (15–17). Additionally, a universal stratification instrument could enhance communication between the ED and the ICU, optimizing a seamless transition of care in chaotic environments. Finally, subsequent sepsis research can stratify findings between higher and lower risk subsets in reporting diagnostic and therapeutic findings, thereby permitting physicians to more effectively apply results to their own populations (Figure 1). EVIDENCE SEARCH Using the TRIP (Translating Research into Practice) database (http://www.tripdatabase.com), the search term “emergency department sepsis score” was entered on December 12, 2008 and identified a secondary review of the validation of the Mortality in the Emergency Department Sepsis (MEDS) score on PUBMED. On PUBMED, the “related articles” tab was selected, yielding 114 citations. Among these results, six were chosen for this critical appraisal. EVIDENCE REVIEW MEDS Derivation Mortality in Emergency Department Sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Critical Care Medicine, 2003 (18).
Population. All adults over age 18 years presenting to Beth Israel Deaconess Medical Center ED (Boston, MA) with suspected infection (as judged by an obtained blood culture) were eligible. In total, 3179 patient encounters were obtained, with 2070 in the derivation cohort and 1109 in the validation cohort. The mean age was 61 years; about 46% of the subjects were men. Study design. From February 2000 through February 2001, ED charts of all patients were reviewed by trained reviewers unaware of the patient’s hospital course on either the day of admission or the next day. No other chart review methods are provided (19,20). Using a modified version of a co-morbid diseaserelated prognosis method to identify subjects with ⬎ 50% likelihood of 30-day mortality, the investigators included “terminal illness” as one candidate variable. SIRS was defined by two or more of the findings in Table 1 (21,22). Severe sepsis was defined as SIRS with organ dysfunction, and septic shock was severe sepsis with fluid-refractory hypotension. Suspected infection was abstracted from the medical decisionmaking portion of the physician documentation and was limited to suspected lower respiratory tract infection, urinary tract infection, intra-abdominal infection, skin or soft tissue infection, and endocarditis. Patients were randomized into a derivation set (two-thirds of cohort) and a validation set (one-third of cohort). Using a logistic regression model, variables associated with the primary outcome were analyzed for independent association with 28-day mortality. Statistical validation of the model was undertaken using the bootstrap method before the model’s prognostic test performance on the validation cohort was evaluated. Finally, investigators analyzed the MEDS score prognostic test performance on the subset of patients more likely to receive aggressive resuscitation by excluding those with fatal disease, dementia, or nursing home residence. Primary outcome. The primary outcome was 28-day hospital mortality. Exclusion criteria. Patients were not eligible if they were under age 18 years or did not have a blood culture obtained in the ED or within 3 h of floor arrival. Main results. In-hospital mortality occurred within 28 days in 110 derivation set patients (5.3%) and 63 validation set patients (5.7% mortality rate). From the 24 variables associated with in-hospital mortality, nine variables were independently associated with the outcome and were used to develop the MEDS score (Table 2). The receiver operating characteristic (ROC)
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EBM – Prognosis Searching for, appraising and applying the best evidence available to assist clinical decisions regarding prognosis and risk assessment. The Prospective Cohort study design produces the highest quality data for analysis in derivation and validation of prognosis estimates. These estimates frequently are presented as outcome scores. Search with a disease keyword with PubMed Clinical Queries search with the “Prognosis” option or the term “prognosis” or “follow up studies.” TRIP Database Medical search engine with emphasis on evidence-based medicine (EBM) and clinical guidelines and queries, including content from Cochrane and Bandolier: www.tripdatabase.com. Logistic Regression A statistical technique that builds a prediction model of an individual’s dichotomous outcome status, for example, mortality, from variables that can be either numerical or categorical. For example, a septic patient’s estimated probability of death in 30 days is found to be associated with age, presence of altered mental status and shock. Kappa A measure of the degree of agreement between observers of a single event adjusted for chance alone. Receiver Operating Characteristic (ROC) Curve A figure that depicts the power of a diagnostic test compared to a reference (gold) standard. The figure typically plots sensitivity (true positive rate) on the vertical axis against 1 – specificity (false positive rate) for different cut-off points for the diagnostic test. The area under the curve (AUC) for a perfect diagnostic test would be 1.0 and 0.5 for one that is no better than chance. Figure 1. Evidence-based medicine teaching points.
area under the curve (AUC) for the derivation set was 0.82, and 0.76 in the validation set. In the validation set, mortality increased with higher MEDS scores, with a range from 1.1% to 39% at the low and high end, respectively. The MEDS score performed equally well in those likely to receive more aggressive care with AUC 0.80.
MEDS Validation Risk stratification of severe sepsis patients in the emergency department. Emergency Medicine Journal, 2006 (23).
investigators included only subjects with severe sepsis as defined by sepsis-related organ dysfunction requiring immediate ICU admission: hypotension, altered sensorium, acute oliguria, or arterial metabolic acidosis. MEDS scores for each patient were then retrospectively calculated and subjects were stratified into high-risk (MEDS 12–27) or low-risk (MEDS ⬍ 12) subsets. Primary outcome. The primary outcome was 28-day hospital mortality rate, although the investigators also evaluated total hospital length of stay and compared the MEDS score ROC curve to the Acute Physiology and Chronic Health Evaluation (APACHE) II score ROC curve (6).
Population. Adult patients admitted from the Shin Kong Wu Ho-Su Memorial Hospital ED (Taipei, Taiwan) to the ICU with severe sepsis were eligible. From 1696 patients admitted to non-surgical ICUs, 276 met inclusion criteria, with mean age 72 years and 45% men.
Exclusion criteria. Patients were not eligible if they were under age 18 years, pregnant, dead on arrival to the ED, suffered multiple trauma before ICU admission, underwent major surgery before ICU admission, or had preexisting do-not-attempt-resuscitation orders documented by treating emergency physicians.
Study design. This was a retrospective non-interventional cohort study between January 2002 and December 2003. Eligible patients were identified from a central electronic database with data abstraction performed by one of two physicians “with extensive experience in chart review procedures” using a standard data collection checklist. The
Main results. Patients were evenly divided between the low-risk (51.8%) and the high-risk (48.2%) groups, but patients with MEDS score ⱖ 12 had significantly higher 28-day mortality (48.9% vs. 17.5%, p ⬍ 0.01). Additionally, the MEDS score had a significantly better discriminatory performance than the APACHE II score (ROC
322 Table 1. Systemic Inflammatory Response Syndrome (SIRS) SIRS is defined as the presence of two or more of the following: Heart rate ⬎ 90 beats/min Respiratory rate ⬎ 20 breaths/min or oxygen saturation ⬍ 90% or need for ⬎ 0.4 FIO2 to maintain saturation Temperature ⬎ 38°C or ⬍ 35.5°C White blood cell count ⬎ 15,000 cells/mm3 or bands ⬎ 10%
area 0.75 vs. 0.26, p ⬍ 0.01). The MEDS score was not associated with hospital length of stay. Performance of severity of illness scoring systems in emergency department patients with infection. Academic Emergency Medicine, 2007 (24). Population. Consecutive adult patients with suspected infection presenting to the Beth Israel Deaconess Medical Center ED (Boston, MA) were eligible. A total of 2132 unique patients were recruited during the study interval, with mean age 61 years and 76% Caucasian. Study design. This was a secondary analysis of a prospective observational cohort between December 2003 and September 2004. Eligible patients were identified via daily review of ED census logs with data collection abstracted thereafter by trained research assistants blinded to the outcome data. Presence of infection was ascertained by analyzing the physicians’ medical decision-making documentation. In calculating the scores, absent or missing data were treated as normal. Investigators computed scores for MEDS, the Confusion Urea Nitrogen Respiratory Rate Blood Pressure 65 Years or Older (CURB65) and the Rapid Emergency Medicine Score (REMS) (25,26). The latter two instruments had been derived for pneumonia and non-surgical ED patients, respectively. Neither had been validated on general ED patients with suspected infections. The REMS was modified (mREMS) because not every subject had a detailed Glasgow Coma Scale score reported.
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Performance of the mortality in emergency department sepsis score for predicting hospital mortality among patients with severe sepsis and septic shock. American Journal of Emergency Medicine, 2008 (27). Population. Subjects were enrolled from Carolinas Medical Center ED (Charlotte, NC) if over age 17 years with suspected or confirmed infection, two or more SIRS criteria, and systolic blood pressure ⬍ 90 mm Hg or mean arterial pressure ⬍ 65 mm Hg after an isotonic fluid bolus or anticipated need for ICU care with lactate ⱖ 4 mmol/L. In total, 143 patients were enrolled, with mean age 58 years, but little other demographic information is provided by which to judge the external validity of this population. Study design. This was a pre-planned secondary analysis of prospectively recruited patients in an early goal-directed therapy (EGDT) trial from August 2004 through November 2006. MEDS score variables were collected prospectively, but scores were not calculated during the clinical encounter. Whether outcome assessors were blinded to the MEDS score is unclear. The investigators also do not clearly state who determined the primary outcome or when it was determined. Primary outcome. The primary outcome was in-hospital mortality. Exclusion criteria. Subjects were excluded if they were under age 17 years, required immediate surgery, or had an absolute contraindication for a chest central venous catheter. Main results. In-hospital mortality occurred in 23%, including 27% pre-EGDT and 18% post-EGDT. The average MEDS score was 10 points. The MEDS score performed poorly overall (AUC 0.61; 95% CI 0.50 – 0.72) and in both the pre-EGDT (AUC 0.69; 95% CI 0.56 – 0.82) and the post-EGDT (AUC 0.53; 95% CI
Primary outcome. The primary outcome was 28-day mortality. Exclusion criteria. None reported.
Table 2. Mortality in Emergency Department Sepsis Score (MEDS) Points
Main results. Eight-three patients died (3.9%; 95% confidence interval [CI] 3.1– 4.7%). As each score increased by one point, so did the odds of death: MEDS 1.4, CURB-65 2.4, mREMS 1.4. Although widely overlapping, MEDS had superior prognostic test performance (AUC 0.85; 95% CI 0.81– 0.89) compared with CURB-65 (AUC 0.79; 95% CI 0.74 – 0.83) or mREMS (AUC 0.80; 95% CI 0.75– 0.85).
Rapidly terminal co-morbid illness Age ⬎ 65 years Bands ⬎ 5% Tachypnea or hypoxemia Shock Platelet count ⬍ 150,000 mm3 Altered mental status Nursing home resident Lower respiratory infection
6 3 3 3 3 3 2 2 2
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0.33– 0.74) subsets. In the moderate-risk groups (MEDS score 5–15), the MEDS score consistently underestimated patient mortality by 14%. Prognostic value of mortality in emergency department sepsis score, procalcitonin, and C-reactive protein in patients with sepsis at the emergency department. Shock, 2008 (28). Population. Consecutive ED patients at Taiwan University Hospital (Taipei, Taiwan) who fulfilled the SIRS criteria with a presumed infectious etiology were eligible. A total of 525 patients were recruited, with a median age of 64 years. Study design. The ED charts of all SIRS patients were reviewed on the day of admission or the next day by one investigator. The authors do not elaborate upon any chart review methods, but they did confirm any missing co-variate via telephone or personal interview (19,20). Terminal illness was defined using the same criteria as Shapiro (18,21). In addition to the clinical data necessary to calculate the MEDS score, investigators also collected blood samples for C-reactive protein (CRP) and procalcitonin (PCT) within 2 h of ED admission to assess the prognostic test characteristics of these inflammatory biomarkers for the sepsisrelated mortality outcomes. Primary outcome. The primary outcome was early (5 day) or late (6 –30 day) all-cause mortality. Exclusion criteria. Subjects were excluded if younger than 15 years, missing data or lost to follow-up, preexisting thyroid disease, or non-infectious etiology of SIRS identified. Main results. After exclusion of 66 subjects left 525 for analysis, the all-cause 30-day mortality rate was 10.5%. Sepsis severity in this cohort was 76% sepsis, 19.4% severe sepsis, and 4.6% septic shock with corresponding mortality 4.3%, 27.5%, and 41.7%, respectively. An elevated CRP (⬎ 60 mg/L) was noted in 41.9% of subjects, and an elevated PCT (⬎ 0.5 ng/mL) was noted in 30.9%. For short-term mortality, the MEDS score had superior prognostic accuracy (c-statistic 0.89) than PCT (0.76) or CRP (0.68). The MEDS score also more accurately identified those at risk for late mortality with C-statistic 0.78 as opposed to PCT 0.70 and CRP 0.63. However, the investigators note that the MEDS score is more specific, but less sensitive than PCT for both early and late mortality, suggesting a complementary role for PCT in screening patients for sepsis-related mortality, with the MEDS score better modeled to confirm high-
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risk suspicions upon the PCT-positive subset. The investigators did not test this hypothesis, however. Validation of the Mortality in Emergency Department Sepsis (MEDS) score in patients with the systemic inflammatory response syndrome (SIRS). Critical Care Medicine, 2008 (29). Population. ED patients at four university hospitals: University of Colorado Hospital, Denver Health Medical Center, Albert Einstein Medical Center, and the University of Pennsylvania. All adult patients meeting SIRS criteria (Table 1) and admitted to the hospital were eligible (22). A total 385 patients were enrolled, with 55% men and median age 56 years. The median hospital length of stay was 5 days, and 11% required mechanical ventilation. Study design. This was a prospective convenience sampling over a 6-month period. Data collection was performed by research assistants or clinical physicians using a uniform closed response instrument. The primary outcome was ascertained by a hospital record review from the index admission without explicit methods or telephone follow-up for discharged patients (19). At one institution, an investigator blinded to the MEDS score abstracted the variables from the medical records to assess the reliability of the prospectively computed score. Investigators used a post hoc logistic regression analysis using the summed MEDS score for each patient as the independent variable and 28-day mortality as the dependent variable to recalibrate a revised MEDS score. Primary outcome. The primary outcome was 28-day allcause mortality. Exclusion criteria. Subjects were excluded if they presented as the result of trauma, were previously enrolled, were a direct admission or transfer from another hospital, or if they were not enrolled within 2 h of ED presentation. The investigators do not provide any details about number of or reasons for exclusions. Main results. Among 385 enrolled patients, 33 (9%; 95% CI 6 –12%) died. The ED diagnosis was available for only 225 (58%) and, of these, 165 (73%) had a source of infection, including 6 (4%) who met the criteria for severe sepsis. In the entire cohort, 184 (48%) were very low, 82 (21%) were low, 82 (21%) moderate, 23 (6%) high, and 9 (2%) very high MEDS mortality scores. The mortality rates associated with the MEDS score were similar to Shapiro’s derivation figures ranging from 0.6% to 40% and increasing progressively. The AUC for
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MEDS (0.88; 95% CI 0.83– 0.92) was superior to the modified MEDS (0.84; 95% CI 0.78 – 0.89) and lactate (0.78; 95% CI 0.66 – 0.90). Terminal illness had moderate reliability ( ⫽ 0.64), but all other MEDS variables had excellent inter-rater reproducibility ( range 0.82– 1.00). Overall, the MEDS score correlation was 0.93 (0.86 – 0.97).
CONCLUSION After validation across prospective samples from multiple institutions, the MEDS score is an accurate and reliable risk-stratification tool for 28-day mortality in ED patients with SIRS. The MEDS score is a Level II clinical decision rule and can therefore be used in various settings with confidence. Some elements of the MEDS score may prove problematic due to interpretation bias (terminal illness) or lack of routine availability (band counts in an era of automated white blood cell counts). Additionally, future inclusion of lactate or other evolving biomarkers may augment the prognostic performance of the MEDS score. The MEDS score lacked prognostic accuracy in the severe sepsis patients, but these are probably not the subset most likely to benefit from the tool because most of these patients will be admitted to the ICU regardless of their score. One recent retrospective application of the APACHE II, Simplified Acute Physiology Score, Mortality Prediction Model, and MEDS suggested that MEDS had the least discriminatory ability in identifying high-risk ED sepsis patients (6,9,30,31). Nonetheless, the MEDS score is currently the superior tool for ED risk-stratification of potentially septic patients and is also associated with long-term mortality (32).
COMMENTARY BY H. BRYANT NGUYEN, MD, MS At the turn of this century, we have now witnessed significant progress in our understanding of the pathogenesis, recognition, and management of sepsis (33,34). As emergency physicians, we have moved beyond simply considering a patient with infection on vasopressors and mechanical ventilation as merely septic. It is crucial that emergency physicians understand the definitions of severe sepsis and septic shock, as early intervention in the ED for this subgroup has been shown to significantly impact outcome. A quandary remains, however, for the bedside clinician in how to best identify and estimate prognosis in these high-risk patients to appropriately intervene. Often, we are presented with a patient similar to our case
scenario. After administering the usual antibiotic and fluid bolus, we are faced with a difficult disposition decision in an elderly patient with a fever, slight bandemia, and suspected bacteremia. The availability of a prognosis prediction tool such as the MEDS score seems prudent. Our patient would have a calculated MEDS score of 11 and a predicted mortality of approximately 9% (Table 3), suggesting that she may require inpatient care. In this case, MEDS seems to be a useful mortality predictor for patients presenting to the ED with suspected sepsis. The score was examined in multiple patient populations and was shown to be accurate in predicting patient mortality. Although MEDS has increased our awareness for sepsis patients in the ED, we need to recognize the limitations in the patient population that comprised the derivation set. The score was originally derived from an ED patient population with a suspected infection as defined by a clinician obtaining a blood culture. The overall mortality for this sample size was a modest 5.3%. This is much lower than the commonly cited 18% mortality for sepsis (1). MEDS therefore seems to accurately predict outcome in the low-risk group of patients in whom a clinician is considering an infectious source. This evidence review also highlights the difference between sepsis, severe sepsis, and septic shock. Sepsis is a systemic response to a local infection, resulting in such signs as fever, tachycardia, tachypnea, leukocytosis, or hyperglycemia. This group of patients may best be prognosticated with MEDS. Severe sepsis includes organ dysfunction or hypoperfusion in the presence of infection. Septic shock occurs when a sepsis patient is refractory to fluid resuscitation, requiring vasopressor therapy. A severe sepsis patient with significant hypoperfusion, such as with lactate ⱖ 4 mmol/L, is also considered in shock, as the criteria of hypotension is no longer required (35). MEDS is an outcome prediction tool for those patients in whom we initially suspect sepsis but not necessarily those patients with severe sepsis or septic shock, in whom we would immediately intervene with EGDT. Only 2.5% of patients in the derivation set presented in septic shock. Lactate was not examined
Table 3. MEDS Score Mortality Estimate
Very low risk Low risk Moderate risk High risk Very high risk
MEDS Score Range
28-Day Mortality Rate (%)*
0–4 5–7 8–12 13–15 ⬎ 15
0.4–11 3.3–5.0 6.6–19 16.1–32.0 39.1–40.0
* Mortality estimates derived from the derivation and validation trials summarized in this review. MEDS ⫽ Mortality in Emergency Department Sepsis.
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nor incorporated as a component of the score. The tool’s creators did not intend MEDS to predict outcome or guide the clinical decisions to initiate intensive therapies such as EGDT in the very high-risk patients. As a result, MEDS consistently underestimates the mortality in those patients who would qualify for EGDT (27,31). The application, therefore, of MEDS in ED patients with suspected sepsis will not allow a clinician to fully risk-stratify patients with significant lactic acidosis or multi-organ failure. For example, if our patient had a lactate level ⬎ 4 mmol/L, her mortality would be at least 28%, instead of 9% as predicted by MEDS (36). There is good evidence that normotensive severe sepsis patients with significant lactic acidosis should receive early antibiotics, hemodynamic monitoring and resuscitation targeting optimal central venous pressure, mean arterial pressure, and central venous oxygenation (37,38). An estimated mortality of 9% per MEDS calculation may not produce adequate concern in the clinician, and this patient may suffer unresolved tissue hypoperfusion. With the barriers surrounding the initiation of intensive therapies in the ED such as EGDT and the sepsis bundle, we still await a prediction tool that can assist clinicians to appropriately risk-stratify patients with severe sepsis or septic shock during their golden hours of presentation (39).
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C. R. Carpenter et al. predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005;45:524 – 8. 37. Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004;32:1637– 42. 38. Arnold RC, Shapiro NI, Jones AE, et al. Multi-center study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock 2008 Dec 22 [Epub ahead of print]. 39. Carlbom DJ, Rubenfeld GD. Barriers to implementing protocolbased sepsis resuscitation in the emergency department—results of a national survey. Crit Care Med 2007;35:2525–32.
The MEDS Score
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ARTICLE SUMMARY 1. Why is this topic important? Estimating short-term mortality in suspected sepsis may facilitate effective allocation of finite critical care resources to a population most likely to benefit. 2. What is the clinical question? Can a risk-stratification tool predict 1-month mortality in emergency department (ED) patients with suspected infection? Search strategy Translating Research into Practice (TRIP) database search using the search term “emergency department sepsis score,” which linked to PUBMED, whereby the related articles tab was used to identify additional findings. Citations Appraised Mortality in emergency department sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Crit Care Med, 2003 (18). Risk stratification of severe sepsis patients in the emergency department. Emerg Med J, 2006 (23). Performance of severity of illness scoring systems in emergency department patients with infection. Acad Emerg Med, 2007 (24). Performance of the mortality in emergency department sepsis score for predicting hospital mortality among patients with severe sepsis and septic shock. Am J Emerg Med, 2008 (27). Prognostic value of mortality in emergency department sepsis (MEDS) score, procalcitonin, and c-reactive protein in patients with sepsis at the emergency department. Shock, 2008 (28). Validation of the mortality in emergency department sepsis (MEDS) score in patients with the systemic inflammatory response syndrome (SIRS). Crit Care Med, 2008 (29). 3. Are the results valid? Yes. MEDS is the only sepsis prognostic screening tool derived and validated in ED populations and has been validated across heterogeneous populations. 4. What are the results? Higher MEDS scores are associated with higher sepsisrelated mortality. MEDS may underestimate mortality in severe sepsis populations. 5. Can I apply the results to my practice? Yes, MEDS is a Level II Clinical Decision Rule. MEDS has not undergone implementation testing to determine if the rapid identification of high-risk subsets will improve patient-important outcomes, clinical efficiency, or cost-effectiveness.