UPDATE IN HOSPITAL MEDICINE FLORIDA CHAPTER ACP MEETING 2016 Himangi Kaushal, M.D., F.A.C.P. Program Director Memorial Healthcare System Internal Medicine Residency
DISCLOSURES None
OBJECTIVES Review some recent literature which impacts our current practice of Hospital Medicine Discuss relevant studies highlighting their strengths and weaknesses Discuss the applicability of the results of these studies
CASE 67 y/o M with PMH of DM-2 and HTN presenting with cough productive of yellow sputum, fever and SOB for 3 days. Temp 102.1; BP 100/70, HR 95, RR 22, 0 2 sat is 92% Alert & oriented Exam consistent with RLL consolidation CXR confirms RLL pneumonia WBC 14,000, BUN 20, CrCl >30 CURB 65 = 2 Inpatient treatment warranted, 30 day mortality = 3%
In Addition To Fluids, Antibiotics And Supportive Care, Which Of The Following Would You Consider To Improve Outcomes? A. High flow oxygen via nasal cannula B. Bronchodilators C. Prednisone D. Statins
BACKGROUND Current IDSA Guidelines (2007) have no recommendation regarding the use of corticosteroids in Community Acquired Pneumonia Hypotensive, fluid-resuscitated patients with severe CAP should be screened for occult adrenal insufficiency (Moderate recommendation; level II evidence)
STUDY SNAPSHOT Study Design Systematic review & Meta Analysis EMBASE, Cochrane and Medline through May 24, 2015 13 randomized control trials (2005 patients)
STUDY SELECTION Included Oral or IV steroids vs. placebo or no treatment Duration of hospitalization Time to clinical stability All cause mortality Need for mechanical ventilation Need for ICU admission Development of ARDS Excluded Ventilator Associated Pneumonia Aspiration Pneumonia Pneumocystis jirovecii pneumonia Studies limited to COPD patients
NNT = 7
RESULTS Outcome Risk Difference Certainty of Evidence All Cause Mortality 2.8% Moderate Need for Mechanical Ventilation 5% Moderate Progression to ARDS 6.2% Moderate Time to Clinical Stability -1.22 days High LOS -1 day High Hyperglycemia 3.5% High GI Hemorrhage NA
LIMITATIONS Limitations Few studies and trials for many events Exclusions Aspiration pneumonia VAP Pneumocystis jerovecii pneumonia GI bleed in prior 3 months Immunosuppression Pregnancy Variable Dose/Duration of steroids 20 60mg for 3 7 days
LIMITATIONS Limitations Few studies and trials for many events Exclusions Aspiration pneumonia VAP Pneumocystis jerovecii pneumonia GI bleed in prior 3 months Immunosuppression Pregnancy Variable Dose/Duration of steroids 20 60mg for 3 7 days
CONCLUSIONS In adults hospitalized with CAP, corticosteroids reduce Length of stay Need for mechanical ventilation ARDS increase Hyperglycemia All cause mortality benefit Needs further study
TAKE HOME MESSAGE In high-risk patients with severe CAP, clinicians may consider use of 0.5 mg/kg of prednisone for 5-7 days with a goal towards reducing morbidity & LOS
LOOK OUT FOR The ADRENAL 1 and ESCAPe 2 trials are currently assessing the efficacy of steroids in 3800 patients with sepsis and 1450 patients with severe CAP, respectively, and will finish data collection in 2016. We should await the pooled results of these trials before we change national standards of care. 1. ADjunctive corticosteroid treatment IN critically ill Patients with Septic Shock (ADRENAL). ClinicalTrials.gov NCT01448109. 2. Extended Steroid in CAP(e)(ESCAPe). VA Clinical Study Protocol #574. ClinicalTrials.gov NCT01283009.
CASE 67 y/o M with PMH of DM-2 and HTN presenting with cough productive of yellow sputum, fever and SOB for 3 days. Temp 102.1; BP 100/70, HR 95, RR 22, 0 2 sat is 92% Alert & oriented Exam consistent with RLL consolidation. CXR confirms RLL pneumonia WBC 14,000, BUN 20, CrCl >30 CURB 65 = 2 Inpatient treatment warranted, 30 day mortality = 3%.
Which Of The Following Might Be An Acceptable Antibiotic Choice For This Patient? 1. Fluoroquinolone Monotherapy 2. Beta-lactam Monotherapy 3. Beta-lactam & Macrolide dual therapy 4. 1 & 3 5. 1, 2 & 3
BACKGROUND Current guidelines for CAP recommend combination therapy in non ICU setting with macrolides in combination with beta lactam or monotherapy with Fluoroquinolones Combination therapy was largely based on observational evidence Resistance is increasing to Fluoroquinolones and macrolides Mandell LA, Wunderink RG, Anzueto A, et al. IDSA/ATS consensus guidelines on the management of community acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27
STUDY SNAPSHOT Study Design Cluster, randomized, cross over *, non-inferiority trial Intention-to-treat * (strategies changed every 4 months) Inclusion Criteria Clinical Criteria Radiologically confirmed pneumonia Exclusion Criteria Patients recently hospitalized (for >48 hours in the previous 2 weeks) Residents of long-term care facilities
STUDY SNAPSHOT Intervention strategies Beta-lactam Beta-lactam macrolide Fluoroquinolone 656 739 888 Primary outcome 90 day all cause mortality
INTENTION TO TREAT ANALYSIS
STRATEGY ADHERENT ANALYSIS
ANTIBIOTIC ADHERENT ANALYSIS
RESULTS Beta lactam antibiotics alone were non-inferior to the combination choice or Fluoroquinolones alone for the primary outcome Up to 30% of patients had their antibiotics switched from the initial strategy in the beta lactam, or beta lactam macrolide group, and only 20% in the Fluoroquinolone group
LIMITATIONS Physicians had discretion to adjust antibiotic regimen based on clinical course NEJM study also confirmed low rates of Legionella, Chlamydia and Mycoplasma at 1.4%, 0.4%, and 1.9%, respectively 40% with an identifiable pathogen in this study, with 30% viral in etiology, and only 2.1% with atypical organisms.
LIMITATIONS Physicians had discretion to adjust antibiotic regimen based on clinical course NEJM study also confirmed low rates of Legionella, Chlamydia and Mycoplasma at 1.4%, 0.4%, and 1.9%, respectively 40% with an identifiable pathogen in this study, with 30% viral in etiology, and only 2.1% with atypical organisms.
CONCLUSION Among patients with clinically suspected CAP admitted to non-icu wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was non-inferior to strategies with a beta-lactam macrolide combination or Fluoroquinolone monotherapy with regard to 90-day mortality.
TAKE HOME MESSAGES Beta lactam monotherapy may be a viable option for patients with CAP not requiring admission to the ICU Promotes antibiotic stewardship and reduces resistance and cost Take into account local antibiograms Superiority trials need to confirm and re-iterate these findings before we can make it standard of care
CASE Unfortunately, your patient s condition takes a turn for the worse. He becomes tachypneic and hypoxemic and is transferred to the ICU. His ABG shows 7.44/30/55 on 2L NC. What would be the best strategy to improve his oxygenation?
What Would Be The Best Strategy To Improve His Oxygenation? 1) NIPPV 2) High flow oxygen 3) Intubation and Mechanical ventilation 4) Put him in a hyperbaric chamber 5) Do nothing! Oxygenation is overrated.
BACKGROUND Noninvasive ventilation lowers mortality, nosocomial infections and intubation rates in patients with COPD or cardiogenic pulmonary edema In hypoxemic respiratory failure, the benefit has been inconsistent High Flow Nasal Cannula (HFNC) About 50L/min of high concentration heated, humidified O 2 May lower dead space Increases excretion of CO2 More comfortable then masks of NIPPV
STUDY SNAPSHOT Study Design Randomized, multicenter trial, 23 ICU s (France & Belgium) 2011 13 Intention-to-treat analysis Inclusion Criteria Age > 18 1. RR > 25 2. PaO 2 / FiO 2 < 300 * 3. No clinical Hx. of Chronic Respiratory Failure Exclusion Criteria Paco2 >45 mm Hg Exacerbation of Asthma or Chronic Resp. failure Cardiogenic Pulmonary Edema, GCS < 12, DNI, C/I to NIPPV
STUDY SNAPSHOT Group Assignments High Flow O 2 Standard O 2 NIPPV 106 94 110 Outcomes: Primary need for intubation at 28 days. Secondary mortality in ICU, at 90 days, ICU LOS, ventilator free days
INCIDENCE OF INTUBATION OVER TIME OVERALL POPULATION
INCIDENCE OF INTUBATION OVER TIME PaO 2 : FiO 2 < 200 mm Hg
PROBABILITY OF SURVIVAL OVER TIME
RESULTS The intubation rate was reduced in the high flow oxygen group vs. the standard oxygen and noninvasive groups, but not statistically significant High Flow O 2 Standard O 2 NIPPV 38% 47% 50% * Mortality rate at 90 days High Flow O 2 Standard O 2 NIPPV 12% 23% 31% * * p= 0.02
LIMITATIONS Low Power (Intubation rates were lower than expected) Trial couldn t be blinded Primary outcome did not reach statistical significance > 80% patients had pneumonia Noninvasive ventilation patients wore the mask for an average of 8 hours/day - were receiving high flow O 2 while off
LIMITATIONS Low Power (Intubation rates were lower than expected) Trial couldn t be blinded Primary outcome did not reach statistical significance > 80% patients had pneumonia Noninvasive ventilation patients wore the mask for an average of 8 hours/day - were receiving high flow O 2 while off
CONCLUSIONS Treatment with high-flow oxygen improved the survival rate among patients with acute hypoxemic respiratory failure No difference in the primary outcome (intubation rate) was observed with high flow oxygen therapy, as compared with standard oxygen therapy or noninvasive ventilation
TAKE HOME MESSAGES HFNC appears safe and effective for spontaneously breathing patients with acute hypoxemic respiratory failure NIPPV still appropriate for COPD/CO2 retention (not an oxygen problem but a problem with too much CO2) Less expensive (< $100/day vs. > $1,000/day)