Download - Update in Hospital Medicine 2017 - Dalhousie University · 2020-06-11 · Pollack CV Jr,et al N Engl J Med. 2017;377(5):431. Epub 2017 Jul 11. • Idarucizumab • Monoclonal antibody

Update in Hospital Medicine 2017

Elizabeth Burton, MD, CCFP

Hospitalist, QE II Health Science Centre,

Halifax, NS

September 30, 2017

15th Annual

Canadian Society of Hospital Medicine

Faculty/Presenter Disclosure:

• Faculty: Elizabeth Burton

• No Relationships with commercial interests

Methodology

• Journal search:

• NEJM

• Annals of Internal Medicine

• JAMA/ JAMA Internal Medicine

• BMJ

• Lancet

• The Hospitalist

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

• 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

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

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

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

• Conclusions:

• No harm and possible benefit to start feeds within

48 hours of admission for mild-moderate

pancreatitis

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

Ms. GI:

• No SIRS criteria

• Mild acute pancreatitis

• Would consider early feeding within 48 hours of

admission

Case 2Mr. 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

• 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

• 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?

Prevalence of Pulmonary Embolism among Patients Hospitalized for SyncopePaolo Prandoni, et al, for the PESIT Investigators*

N Engl J Med 2016; 375:1524-1531October 20, 2016DOI: 10.1056/NEJMoa1602172

• 11 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

http://www.nejm.org/toc/nejm/375/16/

• 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 14.2-20.5%]

• 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




• 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






• Conclusions:

• Important to consider PE in new, isolated

syncope

• D-dimer use


Back to Mr. PE:

• CT PE protocol confirmed PE

• Started on Dabigatran 150mg po BID

• AND…..

Mr. PE at 0300 few days later:

• Acute onset Hematemesis

• Vitals: HR: 130, BP 60/40, RR 24, T 36.6

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

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



• >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 10-30 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



• 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



• 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



• 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 12-24 hours

in 114 patients (redistribution of unbound

dabigatran from extravascular to intravascular

compartment). Bleeding in only 10 patients.

Repeat dosage can be given.



• Patients on Dabigatran annual rates of:

• Life threatening bleeding:1.25-1.5%

• Emergency surgery:1.5%

• Cost

• Factor to consider when counselling

Mr. PE

• Received emergent resuscitation, medications

including Idarucizumab and upper endoscopy

with local treatment of bleeding PUD

• Stabilized and recovered

Case 3Mr.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

• Any other medication or supplement you would

want to consider in the management of this patient?

Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression AnalysisNicole T. Shen, et al. Gastroenterology 2017;152:1889–1900

• 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: 0.30-0.57]


• 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 [0.22-0.48]

• >2 days: RR 0.70 [0.40-1.23]


• 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

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

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

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”

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):546-553. doi:10.1001/jamainternmed.2016.9045 Published online February 6, 2017.

• 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

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):546-553. doi:10.1001/jamainternmed.2016.9045 Published online February 6, 2017.

• 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 0.74-0.98)

• Mild-moderate: no difference metronidazole vs vancomycin

• Severe: Reduced mortality with vancomycin (adjusted RR 0.79, 95% CI 0.65-0.97)

• Conclusion:

• Provides ongoing support that severe CDI should be treated with vancomycin

Mr. CD Conclusion:

• Given age, WBC count, low albumin: you treat

with vancomycin

• You know he’s alive in 30 days because he is re-

admitted again with Functional decline.

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

Questions?