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Supplemental Table 1. Feature DefinitionsTypeFeatureDefinitionVital signsGCSGlasgow coma scaleHeart rateHeart rateHypotensionAny of systolic blood pressure < 90 mmHg, mean arterial pressure < 65 mmHg, or at least a 40 mmHg decrease in systolic blood pressure in 15 minutesRespiratory rateRespiratory rateTemperatureTemperatureLaboratory measurementsBandsNeutrophilic band cellsBilirubinBilirubinCreatinineCreatinineINRInternational normalized ratioLactateLactateMetabolic encephalopathyAny of potassium > 6.0 mEq/L, calcium > 10.5 mg/dL, sodium > 145 mEq/L, glucose < 70 mg/dL or > 200 mg/dLPlateletsPlateletsPTTPartial thromboplastin timeWBCWhite blood cell countMedications and OrdersAnesthesiaAny of propofol, thiopental sodium, desflurane, sevoflurane, propoven, pentothal, midazolam, methoxyflurane, isoflurane, ketamine, halothane, amidate, etomidate, brevital, methohexital, enflurane, diprivan, ethernhalant, ethrane, enflurane, fospropofolAntibioticsAny of amikacin, gentamicin, neomycin, tobramycin, dapsone, rifampin, cefotaxime, azithromycin, aztreonam, ceftazidime, cefuroxime, vancomycin, colistimethate, moxifloxacin, trimethoprim, ciprofloxacin, cefepime, ceftriaxone, ciprofloxacin, gentamicin, levofloxacin, meropenem, metronidazole, moxifloxacin, piperacillin tazobac, vancomycin, piperacillin tazobactam, amoxicillin, ampicillin, ampicillin sulbactam, cefazolin, cefotetan, ceftaroline, ceftolozane tazobactam, clindamycin, daptomycin, doxycycline, ertapenem, erythromycin,linezolid, minocycline, oxacillin, penicillin, polymyxin B, quinupristin dalfopristin, tigecyclineAnticoagulantsAny of apixaban, dabigatran, dalteparin, edoxaban, enoxaparin, fondaparinux, heparin, rivaroxaban, warfarinAnticonvulsantsAny of topiramate, zonisamide, brivaracetam, carbamazepine, clobazam, clonazepam, divalproex, eslicarbazepine, lorazepam, magnesium sulfate, midazolam, ethosuximide, ethotoin, ezogabine, felbamate, fosphenytoin, gabapentin, lacosamide, lamotrigine, levetiracetam, mephenytoin, mephobarbital, methsuximide, oxcarbazepine, paramethadione, perampanel, phenacemide, phenytoin, pregabalin, primidone, rufinamide, tiagabine, topiramate, trimethadione, valproate sodium, valproic acid, vigabatrin, zonisamide, diazepamAntipsychoticsAny of haloperidol, olanzapine, quetiapine, risperidone, trifluoperazineCulture orderAny bacterial culture orderSedativeAny medication indicated as belonging to the therapy class Sedative/Hypnotics in the EHRVasopressorsIV administration of any of dopamine, vasopressin, epinephrine, norepinephrine, neosynephrine. Excludes vasopressors given in the context of a code eventProceduresInvasive ventilationAny invasive mechanical ventilation ordersNoninvasive ventilationAny orders for BiPAP or CPAPSurgical procedureSurgical procedure order including service, procedure name, time, and whether general anesthetic was usedDiagnosesBurnsBurns indicated as chief complaintCerebrovascular accidentAny of ICD-9 433, ICD-10 code I63, or CVA noted in chief complaintDementiaAny of ICD-9 codes 995.52, 785.52 or ICD-10 codes F00, F01, F02, F03, F05.1, G30, G31.1ESRDICD-9 code 585.6 or ICD-10 code N18.6GI bleedPresence of ICD-9 code 578.9, ICD-10 code K92.2, or GI bleeding noted in chief complaintMyocardial infarctionAny of ICD-9 codes 410 or 412 or ICD-10 codes I21, I22, I25.2SeizureChief complaint of seizureSepsis related billing codeAny of ICD-9 codes 995.91, 995.52, 785.52 or ICD-10 codes A41, R65.20, R65.21Sepsis with organ dysfunction billing codeAny of ICD-9 codes 995.52, 785.52 or ICD-10 codes R65.20, R65.21Sleep apneaIndicated by order frequencySuspicion of drug overdose or intoxicationDrug overdose or intoxication noted in chief complaint, naloxone or flumazenil administered, or any of the following lab tests ordered: acetaminophen serum, cocaine, ethanol serum, methadone, salicylate serumTraumaTrauma indicated as chief complaintOtherADT informationCare unit name and admission and discharge timesAgeAgeComfort careCode status order for comfort careDied in hospitalDied in hospitalSupplemental Table 2. Organ Dysfunctions Adjusted by ConfoundersConfounderExcluded Organ Dysfunction IndicatorsSleep apneaNon-invasive ventilation if prescribed for sleep apneaAnticoagulantsINR and PTTGI bleedPlatelets, hypotension, and lactateCVAGCS, hypotension, and lactateSeizureHypotension and lactateAnesthesiaGCSDrug overdose or intoxicationGCS, hypotension, and lactateAntipsychoticsGCSAnticonvulsantsGCSSedativeGCSMetabolic encephalopathyGCSDementiaGCS due to unreliable baselineESRDCreatinineTraumaHypotension and lactateBurns Hypotension and lactateOrgan dysfunction onset within 2 hours prior to 72 hours after surgeryAllAntibiotics initiated within 2 hours prior to 48 hours after surgeryAllINR: international normalized ratio, PTT: partial thromboplastin time, GI: gastrointestinal, CVA: cerebrovascular accident, GCS: Glasgow Coma Scale, ESRD: end-stage renal diseaseSupplemental Table 3. Hospital Population Characteristics?HCGHJHHBMCOverallEncounters (ED & Hospital)103,75282,76646,734233,252Median age (years)62 (IQR: 48-75)59 (IQR: 46-69)60 (IQR: 46-72)60 (IQR: 46-71)Gender (% female)57%51%53%54%Discharged from ED (% of encounters)67%41%47%54%ED Discharge with Sepsis*1%1%1%1%Died in-hospital (% inpatient admits)$560 (2%)836 (2%)521 (2%)1,917 (2%)Hospital Days, Median (IQR)2 (IQR:1-4)3 (IQR: 1-6)3 (IQR: 1-5)3 (IQR: 1-5)Ever in ICU 8%22%19%17%ICU Days, Median (IQR)2 (IQR: 1-3)1 (IQR: 1-3)2 (IQR: 1-4)2 (IQR: 1-3)* Sepsis per any of the definitions studied$ Mortality calculated as inpatient deaths / hospitalized patientsED: emergency department, IQR: interquartile ratio, ICU: intensive care unit, HCGH: Howard County General Hospital, JHH: Johns Hopkins Hospital, BMC: Bayview Medical Center Supplemental Table 4. Percent of Encounters with Vital Signs and Laboratory Value Measurements ObservedMeasurementPercent of Encounters with this measurement (n=233,252)Blood pressure, noninvasive93%Blood pressure, invasive4%Temperature93%Heart rate94%Respiratory Rate93%Glasgow coma scale56%Bilirubin87%Calcium98%Creatinine98%Glucose98%International normalized ratio30%Lactate21%Neutrophilic band cells4%Platelets98%Potassium96%Partial thromboplastin time20%Sodium98%White blood cell count98%Supplemental Table 5. Sensitivity and predictive value of different definitions of sepsis using billing codes as a point of reference by hospitalDefinitionHospitalTotal EncountersBCSBCPVIn-hospital deaths (%)ICU LOS ≥ 3 days (%)Billing codeHCGH862N/A176 (20%)336 (39%)JHH669213 (32%)423 (63%)BMC519139 (27%)325 (63%)SEP-1HCGH54560.920.15381 (7%)769 (14%)JHH66800.970.10450 (7%)1538 (23%)BMC41020.970.12319 (8%)1327 (32%)Sepsis-3HCGH78960.930.10404 (5%)1011 (13%)JHH130740.980.05699 (5%)2864 (22%)BMC52890.970.09394 (7%)1786 (34%)ASEHCGH18940.690.31227 (12%)475 (25%)JHH20210.820.27406 (20%)984 (49%)BMC14720.770.27262 (18%)762 (52%)ESPHCGH22880.870.33270 (12%)561 (25%)JHH19220.940.33373 (19%)870 (45%)BMC16070.930.30275 (17%)793 (49%)BCS: billing code sensitivity, BCPV: billing code predictive value, ICU: intensive care unit, LOS: length of stay, SEP-1: The Centers for Medicare and Medicaid sepsis core measure definition, ASE: Centers for Disease Control Adult Sepsis Event toolkit definition, ESP: EHR-based sepsis phenotypingSupplemental Figure 1. Physician Case Review FlowchartSupplemental Figure 1. This flowchart shows the case review process. Cases identified by the EHR-based Sepsis Phenotyping method were surfaced to physicians as potential sepsis cases. Physicians were asked the questions in the rectangular boxes and based on their answers the patient was indicated as having sepsis confirmed or not having sepsis. ................
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