RESUMEN
PURPOSE: Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes. METHODS: This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up. RESULTS: Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications. CONCLUSIONS: In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.
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Infecciones Comunitarias Adquiridas , Neumonía , Adulto , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Enfermedad Crítica/terapia , Humanos , Metilprednisolona/uso terapéutico , Neumonía/tratamiento farmacológico , Respiración Artificial , Resultado del TratamientoRESUMEN
INTRODUCTION: COVID-19 disease progresses through a number of distinct phases. The management of each phase is unique and specific. The pulmonary phase of COVID-19 is characterized by an organizing pneumonia with profound immune dysregulation, activation of clotting, and a severe microvascular injury culminating in severe hypoxemia. The core treatment strategy to manage the pulmonary phase includes the combination of methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+ protocol). The rationale for the MATH+ protocol is reviewed in this paper. AREAS COVERED: We provide an overview on the pathophysiological changes occurring in patients with COVID-19 respiratory failure and a treatment strategy to reverse these changes thereby preventing progressive lung injury and death. EXPERT OPINION: While there is no single 'Silver Bullet' to cure COVID-19, we believe that the severely disturbed pathological processes leading to respiratory failure in patients with COVID-19 organizing pneumonia will respond to the combination of Methylprednisone, Ascorbic acid, Thiamine, and full anticoagulation with Heparin (MATH+ protocol).We believe that it is no longer ethically acceptable to limit management to 'supportive care' alone, in the face of effective, safe, and inexpensive medications that can effectively treat this disease and thereby reduce the risk of complications and death.
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Ácido Ascórbico/farmacología , Tratamiento Farmacológico de COVID-19 , COVID-19 , Protocolos Clínicos , Heparina/farmacología , Metilprednisolona/farmacología , Tiamina/farmacología , Antiinflamatorios/farmacología , Anticoagulantes/farmacología , COVID-19/sangre , COVID-19/metabolismo , COVID-19/fisiopatología , Humanos , Gravedad del Paciente , SARS-CoV-2 , Vitaminas/farmacologíaRESUMEN
In December 2019, COVID-19, a severe respiratory illness caused by the new coronavirus SARS-CoV-2 (COVID-19) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies' recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working," the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically. The review concludes with a comparison of published multi-national mortality data with MATH+ center outcomes.
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Tratamiento Farmacológico de COVID-19 , Protocolos Clínicos , Unidades de Cuidados Intensivos/organización & administración , Neumonía Viral/tratamiento farmacológico , Ácido Ascórbico/uso terapéutico , COVID-19/epidemiología , Quimioterapia Combinada , Heparina/uso terapéutico , Hospitalización , Humanos , Metilprednisolona/uso terapéutico , Neumonía Viral/epidemiología , Respiración Artificial , SARS-CoV-2 , Tiamina/uso terapéuticoRESUMEN
BACKGROUND: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. METHODS: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. RESULTS: Findings are reported as MP (nâ =â 83) vs control (nâ =â 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (Pâ =â .07) and 14 vs 26 (Pâ =â .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0â ±â 9.0 vs 17.5â ±â 12.8; Pâ =â .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (Pâ =â .84). CONCLUSION: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.
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Corticoesteroides/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Corticoesteroides/administración & dosificación , COVID-19 , Infecciones por Coronavirus/mortalidad , Humanos , Pandemias , Neumonía Viral/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2Asunto(s)
Antiinflamatorios/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Homeostasis/efectos de los fármacos , Neumonía Viral/tratamiento farmacológico , Betacoronavirus/efectos de los fármacos , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Biomarcadores/sangre , COVID-19 , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/metabolismo , Síndrome de Liberación de Citoquinas/virología , Citocinas/antagonistas & inhibidores , Citocinas/genética , Citocinas/inmunología , Esquema de Medicación , Regulación de la Expresión Génica , Homeostasis/inmunología , Humanos , Hidrocortisona/sangre , Inmunidad Innata/efectos de los fármacos , Inflamación/prevención & control , FN-kappa B/genética , FN-kappa B/inmunología , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/metabolismo , Neumonía Viral/virología , SARS-CoV-2 , Estrés Fisiológico , Resultado del Tratamiento , Vitaminas/sangreAsunto(s)
Ventilación no Invasiva/métodos , Insuficiencia Respiratoria/terapia , Aniversarios y Eventos Especiales , Insuficiencia Cardíaca/terapia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Ventilación con Presión Positiva Intermitente/historia , Ventilación con Presión Positiva Intermitente/métodos , Ventilación no Invasiva/historia , Enfermedad Pulmonar Obstructiva Crónica/terapia , Síndrome de Dificultad Respiratoria/terapiaRESUMEN
OBJECTIVES: In the Acute Respiratory Distress Syndrome Network randomized controlled trial, methylprednisolone treatment was associated with increased return to mechanical ventilation with partial loss of early improvements. We hypothesize a causal relationship between protocol-driven rapid discontinuation of methylprednisolone post extubation and return to mechanical ventilation. To explore this possibility, we investigated the timing that events occurred in each treatment arm during active treatment intervention (efficacy) and after stopping therapy. DESIGN AND SETTINGS: Retrospective intention-to-treat analysis of multicenter randomized controlled trial. PATIENTS AND INTERVENTIONS: Patients were randomized to methylprednisolone (2 mg/kg/d) or placebo (89 vs 91). The target sample size was reduced post hoc and provided 80% power for an optimistic 50% mortality reduction. MEASUREMENTS AND MAIN RESULTS: Findings are reported as methylprednisolone versus placebo. By day 28, fewer patients died before achieving extubation (15.7% vs 25.3% and risk ratio, 0.62; 95% CI, 0.34-1.13), more achieved successful extubation (71.9% vs 49.5% and risk ratio, 1.45; CI, 1.14-1.85), time to successful extubation was shorter (hazard ratio, 2.05; CI, 1.42-2.96), and more were discharged alive from the ICU (65.2% vs 48.3%; risk ratio, 1.35; CI, 1.04-1.75). After treatment discontinuation, more methylprednisolone-treated patients returned to mechanical ventilation (26.6% vs 6.7%; risk ratio, 3.98; CI, 1.24-12.79)-consistent with reconstituted systemic inflammation in the presence of adrenal suppression. Participants returning to mechanical ventilation without reinstitution of methylprednisolone had increased risk of ventilator dependence and mortality. Despite loss of early benefits, methylprednisolone was associated with sizable and significant improvements in all secondary outcomes and reduction in serious complications (shock and severe infections). CONCLUSIONS: During active intervention, methylprednisolone was safe and effective in achieving disease resolution. Our findings support rapid glucocorticoid discontinuation post extubation as likely cause of disease relapse. Gradual tapering might be necessary to preserve the significant improvements achieved during methylprednisolone administration.
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Corticoesteroides/uso terapéutico , Metilprednisolona/uso terapéutico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Extubación Traqueal , Humanos , Análisis de Intención de Tratar , Síndrome de Dificultad Respiratoria/mortalidad , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Coinfección , Infección Hospitalaria , Sepsis , Crecimiento y Desarrollo , Humanos , Inflamación , Unidades de Cuidados IntensivosRESUMEN
Background: Our aim was to evaluate the benefits and harms of adjunctive corticosteroids in adults hospitalized with community-acquired pneumonia (CAP) using individual patient data from randomized, placebo-controlled trials and to explore subgroup differences. Methods: We systematically searched Medline, Embase, Cochrane Central, and trial registers (all through July 2017). Data from 1506 individual patients in 6 trials were analyzed using uniform outcome definitions. We investigated prespecified effect modifiers using multivariable hierarchical regression, adjusting for pneumonia severity, age, and clustering effects. Results: Within 30 days of randomization, 37 of 748 patients (5.0%) assigned to corticosteroids and 45 of 758 patients (5.9%) assigned to placebo died (adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], .46 to 1.21; P = .24). Time to clinical stability and length of hospital stay were reduced by approximately 1 day with corticosteroids (-1.03 days; 95% CI, -1.62 to -.43; P = .001 and -1.15 days; 95% CI, -1.75 to -.55; P < .001, respectively). More patients with corticosteroids had hyperglycemia (160 [22.1%] vs 88 [12.0%]; aOR, 2.15; 95% CI, 1.60 to 2.90; P < .001) and CAP-related rehospitalization (33 [5.0%] vs 18 [2.7%]; aOR, 1.85; 95% CI, 1.03 to 3.32; P = .04). We did not find significant effect modification by CAP severity or degree of inflammation. Conclusions: Adjunct corticosteroids for patients hospitalized with CAP reduce time to clinical stability and length of hospital stay by approximately 1 day without a significant effect on overall mortality but with an increased risk for CAP-related rehospitalization and hyperglycemia.
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Corticoesteroides/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Tiempo de Internación/estadística & datos numéricos , Neumonía/tratamiento farmacológico , Corticoesteroides/efectos adversos , Factores de Edad , Infecciones Comunitarias Adquiridas/mortalidad , Hospitalización/estadística & datos numéricos , Humanos , Hiperglucemia/etiología , Oportunidad Relativa , Neumonía/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Regresión , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Authors of recent meta-analyses have reported that prolonged glucocorticoid treatment is associated with significant improvements in patients with severe pneumonia or acute respiratory distress syndrome (ARDS) of multifactorial etiology. A prospective randomized trial limited to patients with sepsis-associated ARDS is lacking. The objective of our study was to evaluate the efficacy of hydrocortisone treatment in sepsis-associated ARDS. METHODS: In this double-blind, single-center (Siriraj Hospital, Bangkok), randomized, placebo-controlled trial, we recruited adult patients with severe sepsis within 12 h of their meeting ARDS criteria. Patients were randomly assigned (1:1 ratio) to receive either hydrocortisone 50 mg every 6 h or placebo. The primary endpoint was 28-day all-cause mortality; secondary endpoints included survival without organ support on day 28. RESULTS: Over the course of 4 years, 197 patients were randomized to either hydrocortisone (n = 98) or placebo (n = 99) and were included in this intention-to-treat analysis. The treatment group had significant improvement in the ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and lung injury score (p = 0.01), and similar timing to removal of vital organ support (HR 0.74, 95 % CI 0.51-1.07; p = 0.107). After adjustment for significant covariates, day 28 survival was similar for the whole group (HR 0.80, 95 % CI 0.46-1.41; p = 0.44) and for the larger subgroup (n = 126) with Acute Physiology and Chronic Health Evaluation II score <25 (HR 0.57, 95 % CI 0.24-1.36; p = 0.20). With the exception of hyperglycemia (80.6 % vs. 67.7 %; p = 0.04), the rate of adverse events was similar. Hyperglycemia had no impact on outcome. CONCLUSIONS: In sepsis-associated ARDS, hydrocortisone treatment was associated with a significant improvement in pulmonary physiology, but without a significant survival benefit. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01284452 . Registered on 18 January 2011.
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Hidrocortisona/uso terapéutico , Síndrome de Dificultad Respiratoria/etiología , Sepsis/complicaciones , Anciano , Anciano de 80 o más Años , Análisis de los Gases de la Sangre/estadística & datos numéricos , Método Doble Ciego , Femenino , Mortalidad Hospitalaria , Humanos , Hidrocortisona/administración & dosificación , Infusiones Intravenosas/métodos , Infusiones Intravenosas/estadística & datos numéricos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/mortalidad , Sepsis/tratamiento farmacológico , TailandiaRESUMEN
PURPOSE: To investigate the effect of prolonged glucocorticoid treatment for patients with acute respiratory distress syndrome (ARDS). METHODS: We conducted two sets of intention-to-treat analyses: (1) a primary analysis of individual patients' data (IPD) of four randomized controlled trials (RCTs) which investigated methylprednisolone treatment (n = 322) and (2) a trial-level meta-analysis incorporating four additional RCTs which investigated hydrocortisone treatment in early ARDS (n = 297). We standardized definitions to derive outcomes in all datasets. The primary outcome for the IPD analysis was time to achieving unassisted breathing (UAB) by study day 28. Secondary outcomes included mechanical ventilation (MV) and intensive care unit (ICU)-free days, hospital mortality, and time to hospital mortality by day 28. RESULTS: By study day 28, compared to the placebo group, the methylprednisolone group had fewer patients who died before achieving UAB (12 vs. 29 %; p < 0.001) and more patients who achieved UAB (80 vs. 50 %; p < 0.001). In the methylprednisolone group, time to achieving UAB was shorter [hazard ratio 2.59, 95 % confidence interval (CI) 1.95-3.43; p < 0.001], and hospital mortality was decreased (20 vs. 33 %; p = 0.006), leading to increased MV (13.3 ± 11.8 vs. 7.6 ± 5.7; p < 0.001) and ICU-free days (10.8 ± 0.71 vs. 6.4 ± 0.85; p < 0.001). In those patients randomized before day 14 of ARDS onset, the trial-level meta-analysis indicated decreased hospital mortality (36 vs. 49 %; risk ratio 0.76, 95 % CI 0.59-0.98, I (2) = 17 %, p = 0.035; moderate certainty). Treatment was not associated with increased risk for infections (risk ratio 0.77, 95 % CI 0.56-1.08, I (2) = 26 %; p = 0.13; moderate certainty). CONCLUSIONS: Prolonged methylprednisolone treatment accelerates the resolution of ARDS, improving a broad spectrum of interrelated clinical outcomes and decreasing hospital mortality and healthcare utilization.
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Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/estadística & datos numéricos , Síndrome de Dificultad Respiratoria/mortalidadRESUMEN
OBJECTIVE: Low-dose methylprednisolone therapy in adults with early acute respiratory distress syndrome reduces systemic inflammation, duration of mechanical ventilation, and ICU length of stay. We report a pilot randomized trial of glucocorticoid treatment in early pediatric acute respiratory distress syndrome. DESIGN: Double-blind, placebo-controlled randomized clinical trial. SETTING: Le Bonheur Children's Hospital, Memphis, TN. PATIENTS: Children (0-18 yr) with acute respiratory distress syndrome undergoing mechanical ventilation. INTERVENTIONS: Patients were randomly assigned to steroid or placebo groups within 72 hours of intubation. IV methylprednisolone administered as loading dose (2 mg/kg) and continuous infusions (1 mg/kg/d) on days 1-7 and then tapered over days 8-14. Both groups were ventilated according to the Acute Respiratory Distress Syndrome Network protocol modified for children. Daily surveillance was performed for adverse effects. MEASUREMENTS AND MAIN RESULTS: Thirty-five patients were randomized to the steroid (n = 17, no death) and placebo groups (n = 18, two deaths). No differences occurred in length of mechanical ventilation, ICU stay, hospital stay, or mortality between the two groups. At baseline, higher plateau pressures (p = 0.006) and lower Pediatric Logistic Organ Dysfunction scores (p = 0.04) occurred in the steroid group; other characteristics were similar. Despite higher plateau pressures on days 1 (p = 0.006) and 2 (p = 0.025) due to poorer lung compliance in the steroid group, they had lower PaCO2 values on days 2 (p = 0.009) and 3 (p = 0.014), higher pH values on day 2 (p = 0.018), and higher PaO2/FIO2 ratios on days 8 (p = 0.047) and 9 (p = 0.002) compared with the placebo group. Fewer patients in the steroid group required treatment for postextubation stridor (p = 0.04) or supplemental oxygen at ICU transfer (p = 0.012). Steroid therapy was not associated with detectable adverse effects. CONCLUSION: This study demonstrates the feasibility of administering low-dose glucocorticoid therapy and measuring clinically relevant outcomes in pediatric acute respiratory distress syndrome. Changes in oxygenation and/or ventilation are consistent with early acute respiratory distress syndrome pathophysiology and results of similar clinical trials in adults. We propose and design a larger randomized trial to define the role of glucocorticoid therapy in pediatric acute respiratory distress syndrome.
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Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Análisis de los Gases de la Sangre/estadística & datos numéricos , Niño , Preescolar , Método Doble Ciego , Femenino , Mortalidad Hospitalaria , Humanos , Lactante , Recién Nacido , Infusiones Intravenosas , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/efectos adversos , Oxígeno/administración & dosificación , Oxígeno/sangre , Proyectos Piloto , Respiración Artificial/mortalidad , Respiración Artificial/estadística & datos numéricos , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/fisiopatología , Resultado del TratamientoRESUMEN
Community-acquired pneumonia (CAP) has a significant impact on public health in terms of short-term and long-term morbidity and mortality. Irrespective of microbiological etiology, the host's inability to fully downregulate systemic inflammation is the dominant pathogenetic process contributing to acute and long-term morbidity and mortality in CAP. Glucocorticoids are the natural regulators of inflammation, and their production increases during infection. There is consistent evidence that downregulation of systemic inflammation with prolonged low-dose glucocorticoid treatment in patients with severe sepsis and acute respiratory distress syndrome improves cardiovascular and pulmonary organ physiology. A recent meta-analysis of pooled controlled small trials (n = 970) of patients admitted with CAP found improved short-term mortality in the subgroup with severe CAP and/or receiving >5 days of glucocorticoid treatment. We have expanded on this meta-analysis by including patients with CAP recruited in trials investigating prolonged low-dose glucocorticoid treatment in septic shock and/or early acute respiratory distress syndrome (n = 1,206). Our findings confirm a survival advantage for severe CAP (RR 0.66, 95% confidence interval 0.51-0.84; p = .001). A large randomized trial is in progress to confirm the aggregate findings of these small trials and to evaluate the long-term effect of this low-cost treatment.
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PURPOSE: To improve 2007 Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) severity criteria to predict intensive care unit (ICU) admission in patients hospitalized with pneumonia. METHODS: A composite score that included the 2007 IDSA/ATS criteria for severe pneumonia and additional significant variables identified by recent publications was tested in patients hospitalized with community-acquired pneumonia. RESULTS: Among 787 patients hospitalized with community-acquired pneumonia, 156 (19.8%) required admission to the ICU. We identified one major criterion (arterial pH <7.30), and 4 minor criteria (tachycardia >125 bpm, arterial pH 7.30-7.34, sodium <130 mEq/L and glucose >250 mg/dL) to be associated with ICU admission. Adding arterial pH <7.30 to the 2 2007 IDSA/ATS major criteria increased sensitivity from 61.5% to 71.8% and area under the curve (AUC) from 0.80 to 0.86. Adding in sequence the four minor criteria to the 2007 IDSA/ATS minor criteria, increased sensitivity from 41.7% to 53.8%, and AUC from 0.65 to 0.69. In the new composite score, combining 1 of 3 major criteria with 3 of 12 minor criteria showed a sensitivity of 92.9% and an AUC of 0.88. CONCLUSION: The addition of arterial pH <7.30 to the 2007 IDSA/ATS major criteria improves sensitivity and AUC to identify patients who will require ICU care.