Update in Hospital Medicine 2017

Transcription

1 Update in Hospital Medicine 2017 Elizabeth Burton, MD, CCFP Hospitalist, QE II Health Science Centre, Halifax, NS September 30, 2017

2 15 th Annual Canadian Society of Hospital Medicine Faculty/Presenter Disclosure: Faculty: Elizabeth Burton No Relationships with commercial interests

3 Methodology Journal search: NEJM Annals of Internal Medicine JAMA/ JAMA Internal Medicine BMJ Lancet The Hospitalist

4 Case 1 Ms. GI 56 year old female with epigastric pain, nausea, vomiting with gradual onset over 24 hours. Now unbearable, 9/10 constant pain. No coffee grind emesis, no melena PMH: Generally well, Obesity, no home meds. No previous surgery

5 Vitals: Temp 37.5, HR 88, BP 152/88, RR 18, O2 sat 94%RA Physical exam: Normal cardiorespiratory exam. Tender epigastrium. No edema. No Stigmata of Liver disease Labs: WBC 12, Hgb 148, Lipase 2300, ALT 58, AST 44, Bili 10, trop <14, Cr 80, Urea 11, Electrolytes within normal, CRP 120 ECG: normal sinus rhythm Imaging: CXR: no acute abnormality Abdo US: no cholecystitis, no biliary tract dilation

6 Ms. GI is admitted with acute pancreatitis: NPO, high rate IVF, parentral pain and nausea control. Dietician approaches you the next day and asks what do want to do with her diet? A. Continue NPO B. Feed her

7 Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic Review. Vaughn VM, et al. Ann Intern Med. 2017;166(12):883. Epub 2017 May 16. Systematic review looking at early (<48 hours) or late (>48 hours) feeding in acute pancreatitis. Outcomes: Primary: LOS, mortality, readmission Secondary: feeding tolerance, N/V/abdo pain, necrotizing pancreatitis Extracted data and rated bias in studies Of 1319 citations reviewed: 11 RCTs including 948 patients 7 trials (3 low risk of bias) mild-moderate pancreatitis 4 trials (1 low risk of bias) severe pancreatitis

8 Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic Review. Vaughn VM, et al. Ann Intern Med. 2017;166(12):883. Epub 2017 May 16. Heterogenous feeding protocols (PO, NG, Nasojejunal) No studies showed significant increase in adverse effects or worsening symptoms, regardless of severity with early feeding Mild-moderate pancreatitis: 4 studies (including 2 with low risk bias): reduced LOS with early feeding 3 studies (including 1 with low risk bias): reduced feeding intolerance/n/v/abdo pain with early feeding Severe pancreatitis: 1 study (low risk bias): no difference LOS, mortality, symptoms

9 Conclusions: No harm and possible benefit to start feeds within 48 hours of admission for mild-moderate pancreatitis

10 Severity in Pancreatitis On admission: APACHEII: calculator SIRS criteria: at least 2 of: 1) Temp >38.3 or <36, 2) HR >90, 3)RR >20 or PaCO2 <32, 4)WBC >12 or <4 or >10% bands At 48 hours: Ranson: calculator CRP: cut off 150

11 Ms. GI: No SIRS criteria Mild acute pancreatitis Would consider early feeding within 48 hours of admission

12 Case 2 Mr. PE 77 year old male presented with fall with LOC<1min. No CP, SOB or Abdo pain. Right knee and leg is swollen and sore. PMH: MCI, alcohol use disorder, smoker,?copd, hypertension Vitals: 88/50>>100/60 post fluid HR 115>>105 post fluid RR 24 O2 sat 88% room air

13 Physical Exam Normal cardiac/respiratory/abdominal exam. No focal neurologic finding, mild swelling right lateral knee and lower leg. Good ROM knee Labs Cr 76, WBC 11, Hgb 110, lytes within normal, trop <14, ABG: mild hypoxia CXR: normal Right knee X-ray: no fracture ECG: sinus tachycardia, no ST changes, no heart block

14 Admitting doctor stops BP meds and admits with Falls NYD, likely related to iatrogenic hypotension, alcohol use +/- something else Question: Is there any other important work-up or diagnoses you would consider in this gentleman with syncope?

15 Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope Paolo Prandoni, et al, for the PESIT Investigators* N Engl J Med 2016; 375: October 20, 2016DOI: /NEJMoa Italian hospitals, first episode syncope (regardless if other explanations of syncope) Ruled out if: 1) Negative Wells Score (4 or less) AND 2) Negative D-dimer If not ruled out had CT-PE protocol or V/Q scan or autopsy N= 560 Mean age 76 Transient LOC <1min, not obviously stroke, seizure or head trauma 2 academic/9 non-academic hospitals Excluded if previous syncope, on anticoagulants or pregnant

16 Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope Paolo Prandoni, et al, for the PESIT Investigators* N Engl J Med 2016; 375: October 20, 2016DOI: /NEJMoa Ruled out N=330, 58.9% Scanned patients N= 230, 41.1% PE= 97 patients (61 main pulmonary/lobar artery or perfusion defect >25%) 42.2% of scanned patients 17.3% of entire cohort [CI %] 1 in 6 patients presenting with syncope Data by alternate explanation: 45/355 (12.7%) with alternative explanation for syncope 52/205 (25.4%) with no alternative explanation for syncope

17 Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope Paolo Prandoni, et al, for the PESIT Investigators* N Engl J Med 2016; 375: October 20, 2016DOI: /NEJMoa Clinical features in patients with PE vs those without PE Tachypnea (45.4% vs. 7.1%) Tachycardia (33% vs. 16.2%) Hypotension (36.1% vs. 22.9%) Signs/symptoms DVT (40.2% vs 4.5%) Active Cancer (19.6% vs. 9.9%) 24.7% had NONE of the above clinical features Didn t include ambulatory care patients Within scanned patients (N= 230) 135: positive d-dimer only 3: high Wells score 92: high Wells score and positive d-dimer

18 Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope Paolo Prandoni, et al, for the PESIT Investigators* N Engl J Med 2016; 375: October 20, 2016DOI: /NEJMoa Conclusions: Important to consider PE in new, isolated syncope D-dimer use

19 Back to Mr. PE: CT PE protocol confirmed PE Started on Dabigatran 150mg po BID AND..

20 Mr. PE at 0300 few days later: Acute onset Hematemesis Vitals: HR: 130, BP 60/40, RR 24, T 36.6

21 What is your immediate management? A) Two large bore IVs, Fluid bolus B) Urgent call to ICU/GI C) IV Pantoloc and maybe octreotide D) A new dabigatran reversal agent E) All of the above

22 Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. Idarucizumab Monoclonal antibody fragment developed to reverse anticoagulant effects of dabigatran Multicenter, prospective, open label study 5g IV Idarucizumab to reverse anticoagulation effects of dabigatran in patients who had either: A. Uncontrolled bleeding B. Required urgent procedure

23 Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. >18 years, on dabigatran, bleeding (unstable or need surgery that can not be delayed >8hours) Treatment: 5g IV (two 50ml (2.5g) infusions, no more than 15 min apart) Blood work: Diluted thrombin time or ecarin clotting time (correlate linearly with dabigatran concentration) Baseline, after first infusion, between min after second infusion and at 1,2,4,12 and 24 hours Complete reversal was normal blood work Clinical outcomes: extent of bleeding and hemodynamic stability, severity of bleeding, peri-procedure hemostasis, thrombotic events, death at 90 days

24 Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. N= 503 (Group A: 301, Group B: 202) Median age 78 years Group A: GI Bleeds (45.5%), ICH (32.6%), trauma (25.9%). Major or life threatening bleeding in 88% Maximum percent reversal 100% [CI 100%-100%] at 4 hrs Independent of age, sex, renal function or dabigatran concentration at baseline

25 Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. Group A: median time to hemostasis (when able to determine): 2.5 hours Group B: median time to procedure 1.6 hours. Surgical hemostasis: 93.4% normal, mild 5.1%, moderate 1.5%, severe 0% Mortality : Group A: 13.5 % 30 day, 18.8% 90 day Group B: 12.6% 30 day, 18.9% 90 day Comparison data with warfarin: ICH 50% 30 day mortality warfarin vs 16.3% in this study Thrombotic events: 4.8%within 30 days 6.8% within 90 days

26 Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. Safety data: 23.3% serious adverse effect but felt to be mostly worsening of index event or co-existing conditions. No consistent patterns identified. Delirium, cardiac arrest, septic shock most common Recurrent elevation of clotting time at hours in 114 patients (redistribution of unbound dabigatran from extravascular to intravascular compartment). Bleeding in only 10 patients. Repeat dosage can be given.

27 Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. Patients on Dabigatran annual rates of: Life threatening bleeding: % Emergency surgery:1.5% Cost Factor to consider when counselling

28 Mr. PE Received emergent resuscitation, medications including Idarucizumab and upper endoscopy with local treatment of bleeding PUD Stabilized and recovered

29 Case 3 Mr.CD 78 year old male admitted with fever, cough, increased amount and purulence of sputum and increasing dyspnea PMH: Severe COPD with frequent admissions. Past 12 months on: amoxicillin, doxycycline, cefuroxime X2 Temp 38.1, HR 98, BP 120/72, RR 22, 02 sat 84% room air WBC 11, Hgb 100, Plt 400, Cr 60, lytes within normal CXR: RLL pneumonia Levofloxacin, Prednisone, Atrovent/ventolin, DVT prophylactic Dalteparin, Nicotine Patch

30 Any other medication or supplement you would want to consider in the management of this patient?

31 Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis Nicole T. Shen, et al. Gastroenterology 2017;152: Reviews have provided evidence for the efficacy of probiotics for the prevention of CDI, but currently not recommended on guidelines Systematic review of RCTs for use of probiotics and CDI in hospitalized patients receiving Abx Search identified 1647:19 studies met criteria, total of 6261 patients, Hospitalized patients, >18 years old, oral or IV antibiotics for any reason Probiotics: any strain or dose Common exclusions: pregnant, immunocompromised, ICU, artificial heart valve, pre-existing GI disorder Incidence CDI Probiotics: 1.6% (54 of 3277) Controls: 3.9% (115 of 2984) Pooled RR of CDI in probiotic users 0.42 [CI: ]

32 Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis Nicole T. Shen, et al. Gastroenterology 2017;152: Meta-regression analysis: Probiotics more effective if given closer to the first dose of antibiotics, decrease in efficacy for every day of delay (P<0.04) Probiotics given within 2 days of first antibiotic were more effective (P = 0.02) 2 days or less: RR 0.32 [ ] >2 days: RR 0.70 [ ]

33 Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis Nicole T. Shen, et al. Gastroenterology 2017;152: Safety: no adverse effects in probiotic group Meta-analysis so more studies needed on specific doses, species and formulations Still an off-label use of probiotics

34 Mr. CD PAD 6: liquid stool, abdominal pain + c difficile Vitals: 36.7, HR 92, BP 124/68, RR 16, O2 sats 88% RA WBC 16, albumin 24, Cr 70, lytes within normal

35 How do want to treat the c.diff?: A. Metronidazole 500mg po TID B. Vancomycin 125mg po QID C. Probiotics D. More than one answer is correct

36 C.diff severity Severity considerations: Scoring system (severe = 2 points or more) 1 point for: Age >60, Temp >38.3 degrees, WBC>15, Albumin <25 2 points for: Pseudomembranes on endoscopy or ICU Simplified: WBC>15, albumin <30, Cr> 1.5X normal Or Clinical Judgement

37 Comparative Effectiveness of Vancomycin and Metronidazole for the Prevention of Recurrence and Death in Patients with Clostridium difficile Infection JAMA Intern Med. 2017;177(4): doi: /jamainternmed Published online February 6, Comparison of recurrence and 30 day mortality in metronidazole vs vancomycin for c.diff treatment Retrospective propensity-matched cohort study VA Jan 2005-Dec 2012 Mean age 68.8 years, 95.9% males 2068 vancomycin treated, matched 8069 metronidazole treated 5452 mild-moderate disease, 3130 severe disease

38 Comparative Effectiveness of Vancomycin and Metronidazole for the Prevention of Recurrence and Death in Patients with Clostridium difficile Infection JAMA Intern Med. 2017;177(4): doi: /jamainternmed Published online February 6, Recurrence: mild-moderate: no difference metronidazole vs vancomycin Severe: no difference metronidazole vs vancomycin 30 day mortality: All groups: Reduced mortality with vancomycin (adjusted RR 0.86, 95% CI ) Mild-moderate: no difference metronidazole vs vancomycin Severe: Reduced mortality with vancomycin (adjusted RR 0.79, 95% CI ) Conclusion: Provides ongoing support that severe CDI should be treated with vancomycin

39 Mr. CD Conclusion: Given age, WBC count, low albumin: you treat with vancomycin You know he s alive in 30 days because he is readmitted again with Functional decline.

40 Take home points Pancreatitis Early feeding may reduce LOS in mild-moderate pancreatitis Syncope 1 in 6 first syncope presentations: PE New Reversal agent for Dabigatran available C.diff: Probiotics given to inpatients on antibiotics for any reason may reduce risk of developing c.diff. The earlier they are given, the more benefit. More studies needed. If severe c.diff, vancomycin reduces all cause mortality better than metronidazole

41 Questions?