new approaches in inpatient medicine that might … · the use of innovative therapies in sepsis....

NEW APPROACHES IN INPATIENT MEDICINE

THAT MIGHT CHANGE YOUR PRACTICE

Jack Chase, MD FAAFP FHM

Direc to r o f Opera t ions,

UCSF Fami ly Med ic ine Inpat ien t Serv ice

San F ranc isco Genera l Hosp i ta l

Ass is tan t C l in ica l P ro fessor

UCSF Dept . o f Fami ly and Communi ty Med ic ine

Presentation Goal & Objectives

• Discuss recent innovations which may

impact family medicine across the continuum

of care

• Highlight selected evidence

• Give links to resources for point-of-care use

Disclosures & Acknowledgements

• No disclosures

• Appreciation to Tracy Minichiello (UCSF) for

teaching on anticoagulation at UCSF Hospital

Medicine Update, and to Steven Cohn MD

(Miami) & Nick Fitterman MD (Hofstra) for

teaching on steroids in CAP at SHM National

Conference.

What’s Pnew in Pneumonia?

Mr. Lattimore, a 67 yo man, comes to the office with 3 days of productive cough, dyspnea and fever

• PMHx: weekly wound clinic visits for venous stasis

• CURB-65 = 1 (~2% mortality)

You elect to give outpatient treatment with close follow-up

Questions?

• What kind of pneumonia is this?

• What antibiotics to prescribe?

• Duration of therapy?

• Other EBM treatments?

Healthcare Associated Pneumonia

• 2005 & 2007 ATS/IDSA guideline: different

treatments for CAP, HCAP, HAP, VAP

• based on microbiology studies and assumption that each

diagnosis has distinct organisms, drug susceptibility,

etc.

• 2016 IDSA guidelines remove HCAP

• Studies: HCAP ≈ CAP flora

• Risk for MDR organisms ≈ patient-specific factors (not

simply interaction with healthcare)

Why does it matter?

• Empiric treatment for community-living patients with pneumonia irrespective of recent healthcare exposure

• Shorter courses (5 days) of antibiotics are effective

• New IDSA CAP guidelines coming Summer, 2017!

• Validated MDR organism risk screen, ?new antibiotic recs

OP (uncomplicated) macrolide OR doxycyline

OP (comorbidities)* respiratory FQ or β-lactam + macrolide

Inpatients (non-ICU) Ceftriaxone + macrolide OR doxycycline

‘Roid rage!

• 2005 & 2007 IDSA guidelines: no

recommendation on corticosteroids in

pneumonia

• Consider in septic shock and non-responders to

antibiotics

• 2015: new meta-analysis in Annals of Internal

Medicine evaluates corticosteroids in CAP

Steroids for CAP?

• Meta-analysis of 13 placebo-controlled RCT’s

among inpatients with CAP (N > 2000):

• Decreased mortality (NNT 38, sCAP: NNT 7)

• Lower risk of ARDS (NNT 38)

• Decreased need for mechanical ventilation (NNT 38)

• Decreased length of stay (1-2.9 days less)

Benefit most evident among patients with severe CAP

• Steroids appear to benefit hospitalized patients with severe CAP (eg. hospitalized in ICU)

• Start early! (within 36 hours)

• No consensus on dosing. Trials used short course ≈ COPD exacerbation (eg. prednisone 40mg QD x 5 days)

• Post-discharge patients may be finishing steroids

Why does it matter?

Pneumonia Prevention

• ACIP 2015 immunization guidelines

• Adults > 65 yo and 19-64 with comorbidities* should receive two phase pneumococcal immunization

*Comorbidi t ies: d iabetes mel l i tus, chronic lung or heart d isease, tobacco use, a lcohol ism, chronic l iver d isease or c i r rhosis, funct ional asplenia , cerebrospinal f lu id leaks, or cochlear implant .

• Reduce PPI use (RR 1.5 for CAP, most prominent in f irst month of use). No increase RR with H2B’s.

13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13)

→ 12 months →23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23)

SOFA’s and CVP’s and CVC’s? Oh my!

Ms. Cortez, a 37 yowoman with DM2, drops in to the office with dysuria, flank pain, fever and vomiting.

VS: T39C, 96/54, P126, R26, O2 Sat 98%

Exam: ill, +R CVAT

Questions?

• Next management steps?

• Location of care?

• Risk of adverse outcomes?

Evolution of sepsisSIRS Early Goal Directed

TherapySurviving Sepsis

CampaignProcess Trial

Bone RC et al. Chest 1992 Rivers et al. NEJM 2001 Partnership (IHI, SCCM, ESICM), 2003-present

ProCESS Investigators. NEJM 2014

ACCP/SCCM consensusconference

Open, randomized, partially blinded, single center trial

Expert meta-analytic guideline of existing

publications

Randomized, multi-centertrial in tertiary hospitals

- Defined SIRS, sepsis, severe sepsis, septic shock

- SIRS = two or more of: T > 38°C or < 36°C; HR > 90; R > 20 or PaCO2 < 32; WBC > 12K or < 4K or > 10% bands

- Sepsis = SIRS + infection

- Aggressive & early treatment (IVF, Abx, lactate, CVC for CVP & scVO2, transfusions & vasopressors)

- ↑ oxygen deliveryvia hemodynamics

- ↓ mortality vs standard care by 15%.

- Comprehensive EBM on diagnostic and treatment considerations

- Emphasis on early recognition and treatment

- Popularized sepsis bundle

- EGDT = protocol-based standard therapy = usual carein severe sepsis

- Common elements = early IVF, broad spectrum Abx, lactate and ↑ perfusion

qSOFA and Prognosis

• Quick Sepsis Related Organ Failure Assessment; Seymour et al, JAMA 2016

• Retrospective analysis of 1.3 million EHR encounters in 12 hospitals in Pennsylvania

• 3 variable tool (GCS < 15, RR >22, SBP < 100) = risk of poor outcome in patients with suspected infectionoutside the ICU

• Score > 2 = ↑ ICU LOS & 3-14x mortality

• qSOFA = 3-item risk assessment tool in sepsis

• More predictive than SIRS → who is at high risk?

• Clinical handoffs (eg. from office to ED)

• Prognostication to pts/families re: severity of illness

• Key treatment elements from prior studies:

• Give broad spectrum antibiotics and fluids ASAP

• Lactate & volume/perfusion assessment guides IVF +

interventions

Why does it matter?

Anticoagulation in transition

Mr. Tran, a 72 yo man with atrial fibrillation and HTN is scheduled for partial thyroidectomy for a non-toxic goiter.

CHA2DS2-VASC: 2 (2.2% CVA/yr)

HAS-BLED: 1 (~1% major bleeding/yr)

Meds: warfarin, HCTZ

Questions?

• Perioperative

anticoagulation?

• Bleed risk vs

thrombosis risk?

• Efficacy and

choice of agent?

To Bridge or Not to Bridge?

• Randomized, double blind RCT of 1884 patients at multiple US sites

• Mean CHADS2 score = 2.3, ie. low-moderate risk for CVA; multiple exclusions including for mechanical valves, recent CVA or embolism

• Compared perioperative treatment: LMWH vs placebo in patients with AF on chronic warfarin treatment

Rechenmacher and Fang, JACC 2015

Bridge Trial Results

• No bridging = bridging in prevention of arterial thromboembolism (ie. CVA) over 30 days of follow-up among patients with AF at low-moderate CVA risk.

• Bridging increased major bleeding (OR 3.6).

• N.B. Rate of arterial thromboembolism was low (0.3 -0.4%) and very few high risk patients – patients at high risk for CVA should be considered for bridging on a case-by-case basis.

Ok, I’ll stop bridging in low-moderate

risk AF. Tell me some good news…

• Meta-analysis of 4 RCT’s (2014) comparing warfarin to direct-acting oral anticoagulants (DOAC’s) in treatment of non-valvular AF.

• 71,000+ patients, median follow-up 1.8-2.8 years

• DOAC’s significantly reduced all -cause mortality (NNT = 132), vascular mortality (NNT = 189) and bleeding mortality (NNT = 313).

• DOAC’s = reduced mortality, more non -life threatening GIB, fewer fatal intracranial hemorrhages vs warfarin.

• Evidence that direct-acting oral anticoagulants are superior to warfarin in reducing mortality.

• Using scoring, eg. CHA2DS2-VASC and HAS-BLED allows patient-specific risk:benefit analysis of anticoagulation

• Avoid perioperative anticoagulant bridging in low and most moderate risk AF patients

• Anticoagulation Forum/Centers of Excellence – point-of-care resource for anticoagulation management.

Why does it matter?

Longevity and evidence-based decisions

Ms. McGillicuddy, your 92 yo

primary care patient, is

hospitalized for progressive

weakness and malnutrition.

The hospitalist calls you to

talk with the patient and her

family about care planning.

• PMHx: COPD on 2L home oxygen, CAD s/p PCI and DES 16 years ago, HFrEF, mild dementia, HTN, HLP, osteoporosis, DJD/OA

• Medications: ASA, aricept, plavix, atorvastatin, Vit D, Calcium, metoprolol, furosemide, spironolactone, senna, tylenol

• SHx: Lives with in-home caregiver, uses assistance for

eating, toileting and dressing. Decreased oral intake in

past 6 months.

Care planning discussion

• Hospitalist recommends a feeding tube and a

GI consult for colon cancer screening.

• The patient wants to “feel better”.

• Her family asks “What’s going to help her at

this point in her life?”

Questions?

• Prognosis?

• Impact on

care

planning

www.eprognosis.ucsf.edu

• Prognostication is a primary technique in medicine• Allows risk:benefit analysis of medical decisions appropriate

for a patient’s stage in l ife

• Based on “gestalt”, many medical providers routinely overestimate both longevity and potential benefit of interventions

• Patients/families & providers generally support truthful prognostic disclosure and counseling with emotional support

• ePrognosis = point-of-care tool for evidence-based prognostication, communication and cancer screening recommendations.

Why does it matter?

• Pneumonia : H CAP + steroids + PCV13 & 23 - PPIs

• Sepsis: > 2 = hospital ize, start IVF and Abx now

• Anticoagulation: + DOACs + r isk:benefi t scoring

• and Longevity-Informed Care Planning

Review

References: Pneumonia• Dress le r D . Co r t i cos te ro i ds f o r Hosp i t a l i zed Commun i t y -Acqu i red Pneumon ia — Time t o Change

P rac t i ce? NEJM Jou rna l Wa tch , Dec 2015

• Ebe l l M . CURB -65 And CRB -65 Seve r i t y Sco res Fo r Commun i t y -acqu i red Pneumon ia . Fam i l y P rac t i ce Management , 2006 .

• Ka l i l AC e t a l . Managemen t o f Adu l t s W i t h Hosp i t a l -acqu i red and Ven t i l a t o r -assoc ia t ed Pneumon ia : 2016 C l i n i ca l P rac t i ce Gu ide l i nes by t he I n f ec t i ous D i seases Soc ie t y o f Amer i ca and t he Amer i can Tho rac i c Soc ie t y. C ID , 2016 .

• Kays in A , V ie ra AJ . Commun i t y -Acqu i red Pneumon ia i n Adu l t s : D iagnos i s and Management . AFP, 2016 .

• Lamber t AA e t a l . R i sk o f Commun i t y -Acqu i red Pneumon ia w i t h Ou tpa t i en t P ro ton -Pump I nh ib i t o r The rapy : A Sys temat i c Rev iew and Me ta -Ana l ys i s . PLoS One , 2015 .

• Mande l l LA e t a l . I n f ec t i ous D i seases Soc ie t y o f Amer i ca /Amer i can Tho rac i c Soc ie t y Consensus Gu ide l i nes on t he Management o f Commun i t y -Acqu i red Pneumon ia i n Adu l t s . C ID , 2007 .

• Siem ien iuk RA e t a l . Co r t i cos te ro i d The rapy f o r Pa t i en t s Hosp i t a l i zed w i t h Commun i t y -Acqu i red Pneumon ia . Anna l s I n t Med , 2016 .

• Uranga A e t a l . Du ra t i on o f An t i b i o t i c Trea tmen t i n Commun i t y -Acqu i red Pneumon ia : A Mu l t i cen ter Randomized C l i n i ca l Tr i a l . Jama, 2016 .

References: Sepsis• Bone, RC et al . Defini t ions for Sepsis and Organ Fai lure and Guidel ines for

the Use of Innovat ive Therapies in Sepsis. Chest, 1992.

• Rivers E et al . Early goal -directed therapy in the treatment of severe sepsis

and sept ic shock. NEJM 2001.

• Seymour CW et al . Assessment of Cl inical Cri ter ia for Sepsis For the Third

Internat ional Consensus Defini t ions for Sepsis and Septic Shock (Sepsis -3)

• ProCESS Invest igators. A Randomized Trial of Protocol -Based Care for

Early Septic Shock. NEJM, 2014.

• Internat ional Guidel ines for Management of Severe Sepsis and Septic

Shock: 2012 Surviv ing Sepsis Campaign. Society for Cri t ical Care Medicine,

2012.

References: Anticoagulation

• Douket is JD e t a l . Per iopera t i ve Br idg ing Ant icoagu la t ion in Pat ien ts w i th A t r ia l F ib r i l l a t ion . NEJM 2015.

• L iew A e t a l . Compar ing mor ta l i t y in pa t ien ts w i th a t r ia l f ib r i l l a t ion who are rece iv ing a d i rec t -ac t ing o ra l an t i coagu lant o r war fa r in : a meta -ana lys is o f randomized t r ia ls . J Thromb Haemost , 2014.

• L ip GY e t a l . Ref in ing c l in ica l r i sk s t ra t i f i ca t ion fo r p red ic t ing s t roke and th romboembol ism in a t r ia l f ib r i l l a t ion us ing a nove l r i sk fac to r -based approach: the euro hear t survey on a t r ia l f ib r i l l a t ion . Ches t . 2010.

• Pis te rs R, e t a l . A Nove l User -F r iend ly Score (Has -B led) To Assess 1 -Year R isk Of Ma jor B leed ing In Pat ien ts Wi th A t r ia l F ib r i l l a t ion : The Euro Hear t Survey. Ches t . 2010.

• Rechenmacher SJ , Fang JC. Br idg ing Ant icoagu la t ion : Pr imum Non Nocere . JACC, 2015.

• Sample CHADS2-Vasc2 and HAS BLED ca lcu la to rs : h t tp : / /www.mdca lc .com /

• Ant icoagu la t ion Forum Ant icoagu la t ion Centers o f Exce l lence : h t tp : / /exce l lence.ac fo rum.org /

References: Prognostication• Anderson WG et a l . A Mul t icenter Study o f Key Stakeho lders ’ Perspect ives on

Communicat ing wi th Surrogates about Prognos is in In tens ive Care Uni ts . Ann Amer Thor Soc, 2015.

• Bai le WF et a l . SPIKES—A Six -Step Protoco l fo r De l iver ing Bad News: Appl ica t ion to the Pat ient w i th Cancer. The Onco log is t , 2000.

• Chr is tak is NA, Lamont EB. Extent and determinants of error in physic ians' prognoses in terminal ly i l l pat ients: A prospect ive cohor t s tudy. West J Med, 2000.

• Glare P. A systemat ic review of physic ians' survival predict ions in terminal ly i l l cancer pat ients. BMJ 2003.

• Krouss , M e t a l . Physic ian Understanding and Abi l i ty to Communicate Harms and Benef i ts of Common Medical Treatments. JAMA Intern Med, 2016.

• Yourman MC et a l . Prognost ic Ind ices for O lder Adu l ts : A Systemat ic Rev iew. JAMA 2012.

• ePrognos is .ucsf .edu

Thank You