ARTICLES THAT HAVE CHANGED MY INPATIENT PRACTICE OF MEDICINE

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1 ARTICLES THAT HAVE CHANGED MY INPATIENT PRACTICE OF MEDICINE Melissa (Moe) Hagman, MD, FACP Associate Professor, Internal Medicine/Palliative Medicine SYNCOPE 72 year old otherwise healthy gentleman with CAD is admitted after syncope while standing in church. No palpitations. No prodrome. VS: Afebrile, HR 110, BP 128/76, not orthostatic, SpO 2 98% on RA. Normal physical exam. Clinical Question: What test would you request next? What test would you request next? A. D dimer B. Transthoracic echocardiogram C. Carotid duplex D. Tilt table test 0% 0% 0% 0% A. B. C. D. 1

2 PREVALENCE OF PE IN SYNCOPE Determine prevalence of PE in persons hospitalized for syncope Prospective cross sectional study at 11 hospitals in Italy Adults admitted for first episode of syncope Reasons for Admission: No explanation for syncope identified Severe co existing conditions Care for trauma related to fall High probability of cardiac syncope based on Evaluation of Guidelines in Syncope Study score Prandoni P, et al. N Engl J Med. 2016; 375: EGSYS SCORE Variable Score Palpitations preceding syncope 4 Heart disease and/or abnormal ECG 3 Syncope during effort 3 Syncope while supine 2 Precipitating/predisposing factors 1 (warm and/or crowded place, prolonged orthostasis, fear/pain/emotion) Autonomic prodromes 1 (nausea/vomiting) Total score 3 suggests cardiac syncope, with sensitivity 92% and specificity 69% Del Rosso A, et al. Heart. 2008; 94: PREVALENCE OF PE IN SYNCOPE 330 (59%) negative Wells and D dimer 560 pts, mean age (41%) positive Wells and/or D dimer 133 (58%) negative CT/VQ 97 (42%) positive CT/VQ 24 (25%) normal BP, HR, RR, Phx Ex Prandoni P, et al. N Engl J Med. 2016; 375:

3 SIMPLIFIEDWELLS SCORE Variable Score Clinical signs/symptoms of DVT 3 Alternative diagnosis less likely than PE 3 Heart rate >100 beats/min 1.5 Immobilization or surgery in previous 4 weeks 1.5 Previous venous thromboembolism 1.5 Hemoptysis 1 Active cancer 1 Total score >4 indicates probable PE Total score 4 indicates that PE is unlikely Prandoni P, et al. N Engl J Med. 2016; 375: PREVALENCE OF PE IN SYNCOPE Overall prevalence of PE was 17% PE present in 25% of patients with syncope of unclear cause PE present in 13% of patients with an alternative diagnosis for syncope Prandoni P, et al. N Engl J Med. 2016; 375: AHA GUIDELINES ON SYNCOPE One study showed higher prevalence of pulmonary embolus in older patients with first episode of syncope after admission to the hospital. Further confirmation of this finding in the older populations is warranted. Shen WK, et al. J Am Coll Cardiol Mar 9. [Epub ahead of print] 3

4 PREVALENCE OF PE IN COPD EXACERBATIONS Determine the prevalence, location, and clinical markers of PE in patients with unexplained acute exacerbations of COPD Systematic review and meta analysis 7 studies with total of 880 patients with unexplained COPD exacerbations Pooled prevalence of PE 16% Thrombus location 68% in main pulmonary, lobar, or inter lobar arteries In unexplained COPD exacerbation with PE: Pleuritic CP and signs of acute heart failure more common Signs of respiratory infection less common Aleva FE, et al. Chest. 2016; 151: WHAT I HAVE CHANGED In persons admitted with syncope, I screen for PE with a simplified Well s score and a D dimer. If Well s or d dimer suggest PE, I image for PE. In persons with unexplained COPD exacerbation, I consider the diagnosis of PE, especially in patients with pleuritic chest pain, signs of acute heart failure, and no symptoms of respiratory infection. OXYGEN TARGETS IN THE ICU 76 yo gentleman presents with cough, fever, and SOB. No COPD. VS: T 38.5 C, HR 112, BP 122/74, SpO 2 82% on RA. ABG shows hypoxemia without hypercarbia. CXR shows infiltrate consistent with pneumonia. Clinical Question: What goal SpO 2 are you going to aim for during his ICU stay? 4

5 What goal SpO 2 are you going to aim for during his ICU stay? A. SpO % B. SpO % C. SpO % 0% 0% 0% A. B. C. OXYGEN TARGETS IN THE ICU Assess whether conservative strategy for O 2 supplementation in the ICU improves outcomes Single center, open label, randomized trial Stopped early due to difficulties with enrollment 434 adults admitted to Med/Surg ICU with anticipated length of stay 72 hours Girardis M, et al. JAMA. 2016; 316: OXYGEN TARGETS IN THE ICU Oxygen Therapy Intervention: Target goal PaO mmhg, SpO % Allow PaO 2 up to 150 mmhg, SpO % ICU Mortality (%) PaO 2 Target SpO 2 Target (%) Daily Average (mmhg) PaO Up to Less shock, liver failure, bacteremia with SpO 2 target 94 98% NNT = 12 with conservative SpO 2 goal to prevent 1 death Girardis M, et al. JAMA. 2016; 316:

6 Cardiac Arrest: DANGERS OF HYPEROXIA Post resuscitation hyperoxia is associated with increased mortality NNH = 6 with hyperoxia to contribute to 1 death Acute Myocardial Infarction: Supplemental oxygen therapy harmful to normoxic patients with STEMI NNH = 22 for recurrent in hospital MI, 11 for arrhythmia Critical Illness: Kilgannon JH, et al. JAMA. 2010; 303: Stub D, et al. Circulation. 2015; 131: Meta analysis of the effects of hyperoxia in critically ill adults Hyperoxia = poor hospital outcomes including increased mortality Helmerhorst HJ, et al. Crit Care Med. 2015; 43: WHAT I HAVE CHANGED I will target normoxia in patients in the ICU and with other critical illness such as cardiac arrest or acute MI. Avoid hypoxia. Avoid hyperoxia. NON INVASIVE VENTILATION (NIV) Determine whether NIV via a helmet improves intubation rates compared to NIV via face mask in patients with ARDS Single center randomized trial 83 persons with ARDS and need for NIV 8 hours Excluded if lack of gag reflex or Glasgow Coma Scale <8 Patel BK, et al. JAMA. 2016; 315:

7 NON INVASIVE VENTILATION (NIV) Intervention: Helmet NIV Face mask NIV Outcome Helmet Facemask NNT Ave PEEP (cm H 2 O) Intubation (%) day Mortality (%) Patel BK, et al. JAMA. 2016; 315: HIGH FLOW OXYGEN To determine whether high flow oxygen therapy is non inferior to noninvasive positive pressure ventilation (NPPV) for management of acute hypoxemic respiratory failure Multicenter, open label, randomized, controlled trial 310 adults with acute hypoxic respiratory failure admitted to ICU RR >25/min, PaO 2 /FIO 2 300mmHg while on 10L/min O 2 for >15 minutes, PaCO 2 <45mmHg, no chronic lung disease Frat JP, et al. N Engl J Med. 2015; 372: Intervention Intubation (%) 50L/min High Flow Nasal Cannula HIGH FLOW OXYGEN Vent free Days at 28 days (mean) Death in ICU (%) Death at 90 days (%) L/min Face Mask NPPV NNT with high flow oxygen to prevent one death at 90 days 9 vs face mask 6 vs NPPV Frat JP, et al. N Engl J Med. 2015; 372:

8 WHAT I HAVE CHANGED I will consider use of helmet non invasive ventilation instead of facemask non invasive ventilation for ARDS. I will use high flow oxygen for treatment of acute hypoxic respiratory failure without hypercarbia. OXYGEN FOR MILD TO MODERATE COPD Clinical Question: Which of the following individuals with COPD will likely benefit from supplemental oxygen? Which of these individuals with COPD will likely benefit from supplemental O 2? A. SpO % at rest B. SpO % with activity and no change in 6 min walk distance with supplemental O 2 C. SpO % with activity and no change in 6 min walk distance with supplemental O 2 D. None of the above 0% 0% 0% 0% A. B. C. D. 8

9 OXYGEN FOR MILD TO MODERATE COPD Determine efficacy of O 2 supplementation in patients with stable COPD and resting or exercise induced moderate desaturation Multicenter, randomized controlled trial 738 with stable COPD and resting desaturation, SpO % or exercise induced desaturation, SpO 2 80% for 5 minutes and <90% for 10 seconds during the 6 minute walk test Albert R, et al. N Engl J Med. 2016; 375: OXYGEN FOR MILD TO MODERATE COPD Intervention: Long term supplemental oxygen No supplemental oxygen Supplemental Oxygen Time to Death or First Hospitalization (per 100 person yr) Death (per 100 person yr) First Hospitalization (per 100 person yr) No Yes Follow up 1 6 years No difference in QOL, lung function, 6 minute walk distance Albert R, et al. N Engl J Med. 2016; 375: GOLD 2017 In patients with severe resting chronic hypoxemia, long term oxygen therapy improves survival. In patients with stable COPD and resting or exercise induced moderate desaturation, long term oxygen treatment should not be prescribed routinely. However, individual patient factors must be considered when evaluating the patient s need for supplemental oxygen. Global Initiative for COPD (GOLD)

10 OXYGEN IN 6 MIN WALK TEST FOR COPD Determine effect of supplemental O 2 during exercise Single blind, randomized controlled trial 124 persons with stable COPD Supplemental O2 improved 6 min walk distance to a clinically relevant extent ( 30 meters) in 42% of patients hypoxic at rest (SpO 2 <88%) 47% of patients with exercise induced hypoxia (SpO 2 <88%) Jarosch I, et al. Chest. 2017; 151: WHAT I HAVE CHANGED I no longer fret when COPD patients with resting SpO 2 88% politely decline supplemental O2 for treatment of their hypoxia with exercise. I will consider 6 min walk tests with and without supplemental oxygen in COPD patients with exerciseinduced hypoxia to determine if supplemental oxygen significantly improves exercise tolerance. INTRACRANIALHEMORRHAGE AND ASA 77 yo woman presents with spontaneous intracerebral hemorrhage. Meds: Aspirin 81mg po daily for CAD. VS: Afebrile, HR 86, BP 154/82, SpO 2 98% on RA. Labs: Platelet count 210K. There is no plan for her to have surgery. Clinical Question: Should you transfuse platelets? 10

11 PLATELET TRANSFUSION IN CEREBRAL HEMORRHAGE Determine if platelet transfusion after acute spontaneous cerebral hemorrhage reduces death or dependence in persons on antiplatelet therapy Multicenter, open label, masked endpoint randomized trial 190 adults with non traumatic cerebral hemorrhage, use of antiplatelet therapy for 7 days prior, Glasgow Coma Score 8 Randomized within 6 hours of symptom onset Baharoglu MI, et al. Lancet. 2016; 387: PLATELET TRANSFUSION IN CEREBRAL HEMORRHAGE Intervention: Platelets vs no platelets Platelets were transfused within 90 minutes of brain imaging Outcome Platelets No Platelets NNH Death or Dependence at 3 months (%) Death during Initial Hospitalization (%) Baharoglu MI, et al. Lancet. 2016; 387: PLATELET TRANSFUSION IN GI BLEED Evaluate impact of platelet transfusion in patients taking antiplatelet agents who present with GI bleed Retrospective cohort study 408 adults with platelet counts >100 x 10 9 /L and GI bleed Intervention: Platelet transfusion vs no platelet transfusion Increased mortality (NNH 17), MI, recurrent GIB, and length of stay with platelet transfusion Zakko L, et al. Clin Gastroenterol Hepatol. 2016; 15:

12 INTRACRANIALHEMORRHAGE AND HTN 77 yo woman presents with spontaneous intracerebral hemorrhage. VS: Afebrile, HR 86, BP 188/98, SpO 2 98% on RA. Labs: Platelet count 210K. Clinical Question: What is your goal blood pressure for this woman? What is your goal blood pressure for this woman? A. 110 to 139 mm Hg B. 140 to 179 mm Hg BP CONTROL IN CEREBRAL HEMORRHAGE Determine the efficacy of intensive versus standard antihypertensive treatment initiated within 4.5 hours after symptom onset and continued for the next 24 hours in patients with spontaneous intracerebral hemorrhage Multicenter, randomized, open label trial Discontinued at prespecified interim analysis due to futility 961 adults with supratentorial intracerebral hemorrhage (volume <60cm 3 ), Glasgow Coma Scale 5, systolic BP >180 mmhg Qureshi AI, et al. N Engl J Med. 2015; 375:

13 BP CONTROL IN CEREBRAL HEMORRHAGE Intervention: Nicardipine continuous IV infusion to: Target systolic BP mmhg Target systolic BP mmhg No difference in: Death or dependence at 3 months Hematoma expansion Patient assessment of health measures at 3 months Qureshi AI, et al. N Engl J Med. 2015; 375: AHA/ASA STROKE GUIDELINES For ICH patients presenting with SBP mmhg and without contraindication to acute BP treatment, acute lowering of SBP to 140 mmhg is safe and can improve functional outcome. For ICH patients presenting with SBP >220 mmhg, consider aggressive reduction of BP with a continuous intravenous infusion and frequent BP monitoring. Hemphill JC 3 rd, et al. Stroke Jul;46(7): INTRACRANIAL HEMORRHAGE AND WARFARIN 77 yo woman presents with spontaneous intracerebral hemorrhage. Meds: Warfarin for AFIB. VS: Afebrile, HR 86, BP 160/84, SpO 2 98% on RA. Labs: Platelet count 210K, INR Clinical Question: In addition to vitamin K, what would you use to reverse the warfarin in this woman? 13

14 In addition to vitamin K, what would you use to reverse the warfarin in this woman? A. Nothing else B. Fresh frozen plasma (FFP) C. Prothrombin complex concentrate (PCC) D. FFP and PCC 2017 GUIDELINE REVERSAL OF ANTITHROMBOTICS IN ICH Warfarin reversal: Stop warfarin (unless DIC, life threatening ischemia, etc.) Give vitamin K 10mg IV Favor 4 factor or 3 factor PCC over FFP for rapid reversal Faster and more predictable Less volume overload Cost approximately $5000 for PCC and approximately $70/unit of FFP Check INR approximately 15 mins after PCC and q6hrs thereafter x 24 48hrs Frontera JA, et al. Neurocrit Care. 2016; 24:6 46. WHAT I HAVE CHANGED I do not transfuse platelets for cerebral hemorrhage or GI bleed in persons with normal platelets counts and chronic antiplatelet medication use. I target systolic BP 140 mmhg in patients with acute intracerebral hemorrhage. I consider prothrombin complex concentrate (PCC) rather than fresh frozen plasma (FFP) for rapid reversal of warfarin in life threatening situations. 14

15 RE INITIATION OF WARFARIN AFTER ICH Investigate the prognosis associated with resuming warfarin in hemorrhagic stroke and traumatic ICH Nationwide, observational cohort study 2415 persons with AFIB and hemorrhagic stroke or traumatic ICH Intervention: Resumption of warfarin No warfarin Nielsen PB, et al. JAMA Intern Med. 2017; 177: RE INITIATION OF WARFARIN AFTER ICH Initial Hemorrhage Type Restarted Warfarin Ischemic Stroke (per 100 person yrs) Recurrent ICH (per 100 person yrs) All cause Mortality (per 100 person yrs) Hemorrhagic No Stroke Yes Traumatic No ICH Yes Mean age 77 Mean CHA 2 DS 2 VASC 4, mean HAS BLED = 3.6 All cause mortality at 1 year 25.4% with warfarin, 34.9% without warfarin, NNT 11 Nielsen PB, et al. JAMA Intern Med. 2017; 177: WHAT I HAVE CHANGED With the caveats of observational data, I will have informed decision making discussions with patients considering resumption of warfarin for atrial fibrillation after hemorrhagic stroke or traumatic intracerebral hemorrhage. 15

16 BRIDGE ANTICOAGULATION FOR NONVALVULAR AFIB floatnurse mike.blogspot.cz 58 yo gentleman with chronic nonvalvular AFIB on warfarin presents with cholecystitis. No history of stroke/tia. Warfarin reversed. CHA 2 DS 2 VASC = 5. Headed to the OR. Clinical Question: The surgeon consults you to determine if the patient should have bridging anticoagulation post operatively. Would you recommend bridging anticoagulation in this patient? BRIDGE ANTICOAGULATION NONVALVULAR AFIB Doherty JU, et al. J Am Coll Cardiol. 2017; 69: BRIDGE ANTICOAGULATION AFIB NNT casdcf Doherty JU, et al. J Am Coll Cardiol. 2017; 69: