Update in Hospital Medicine: Turning Evidence into Practice Joseph Li, MD Director, Hospital Medicine Beth Israel Deaconess Assistant Professor of Medicine

Update in Hospital Medicine: Update in Hospital Medicine: Turning Evidence into Turning Evidence into

PracticePractice

Joseph Li, MDDirector, Hospital Medicine Beth Israel DeaconessAssistant Professor of MedicineHarvard Medical School

Jeff Glasheen, MDDirector, Hospital Medicine U. of ColoradoAssociate Professor of MedicineUniversity of Colorado

Update in Hospital Medicine

Update in Hospital Medicine Update in Hospital Medicine 20082008

• Case based format• Focus on breadth rather than depth• Major topic areas: Reviews / short

takesSepsisC. Difficile infectionStrokeACSCAPVTE prophylaxis


Case PresentationCase Presentation

A 63 year old woman with HTN presents with 3 days of fever, cough, and shortness of breath. On admission, she has evidence of septic shock secondary to community-acquired pneumonia.

Blood cultures are drawn and appropriate antibiotics are initiated. Despite an adequate fluid bolus and norepinephrine (Levophed®) infusion at 5 μg/min, she remains hypotensive (MAP < 60mmHg).


A. Start an infusion of phenylephrine (Neo-synephrine®).

B. Increase the infusion of norepinephrine.

C. Administer the pneumococcal vaccine. . . . STAT!

D. Start an infusion of vasopressin.

What is the next best step to increase What is the next best step to increase her mean arterial pressure (MAP)?her mean arterial pressure (MAP)?


VASST: Vasopressin vs. VASST: Vasopressin vs. NorepinephrineNorepinephrine

Question: Does vasopressin decrease mortality compared to norepinephrine in patients with septic shock?

Design: Randomized, double-blind, 778 adults w/ septic shock on norepinephrine; 70% medical/30% surgical

VASST Investigators. NEJM 2008;358:877-87.


ResultsResults

Vasopressin Norepinephrine

Mortality at 28 d

35.4% 39.3%

Mortality at 90 d

43.9% 49.6%

Serious adverse events

10.3% 10.5%

•Trend toward higher rates cardiac arrest with norepinephrine.•Trend toward higher rates digital ischemia with vasopressin.


VASST: Vasopressin vs. VASST: Vasopressin vs. NorepinephrineNorepinephrine

Question: Does vasopressin decrease mortality compared to norepinephrine in patients with septic shock?

Design: Randomized, double-blind, 778 adults w/ septic shock on norepi; 70% medical/30% surgical

Results: No difference in mortality or adverse events.

Conclusion: In pts on norepi for septic shock, no benefit to adding vasopressin; increase the norepi.

Comment: In septic shock, start with fluids, add norepi or dopamine; Vasopressin can be considered as adjunct.VASST Investigators. NEJM 2008;358:877-87.

Surviving Sepsis. Crit Care Med 2008;36:296-327.


A. Start an infusion of phenylephrine (Neo-Synephrine®).

B. Increase the infusion of norepinephrine.

C. Administer the pneumococcal vaccine. . . STAT.

D. Start an infusion of vasopressin.

What is the next best step to increase What is the next best step to increase her mean arterial pressure (MAP)?her mean arterial pressure (MAP)?


Case ContinuedCase Continued

The patient’s hypotension improves with increased norepinephrine but she remains critically ill. Your hospital has a checklist to guide the evidence-based management of sepsis. Fifth on the list says “give steroids.” You sit back in your chair and rub your chin . . .


Regarding the use of steroids in this patient with septic shock, you should:

A. Do a Cosyntropin (ACTH) stimulation test to see if she has a response.

B. Give hydrocortisone 50mg IV Q6o and fludrocortisone 50μg PO once daily.

C. Give hydrocortisone 50mg IV Q6o.

D. Lather topical hydrocortisone 1% to entire body.

E. Scratch it off the list (no steroids at this time).


CORTICUS: Hydrocortisone in Septic CORTICUS: Hydrocortisone in Septic ShockShock

Question: Is low-dose hydrocortisone (HC) effective and safe in patients with septic shock?

Design: Randomized, double-blind, HC vs placebo in 499 pts w/ septic shock; each pt’s adrenal responsiveness to corticotropin was evaluated.

CORTICUS. NEJM 2008;358:111-124.


ResultsResults

No Response to ACTH stim test

Response to ACTH

stim test

All Patients

HC Plac HC Plac HC Plac

Death 28d

39.2 36.1 28.8 28.7 34.3 31.5

Death 1yr

58.9 57.1 55.0 53.2 56.6 54.0

Shock reversal

3.9 6.0 2.8 5.8* 3.3 5.8*

CORTICUS. NEJM 2008;358:111-124.


ResultsResults

Hydrocortisone

Placebo

Hyperglycemia (bs > 150)

85% 72%*

Hypernatremia (Na+ > 150)

29% 18%*

Superinfection

33% 26%**

New septic shock

6% 2%** p < 0.05** Trend

CORTICUS. NEJM 2008;358:111-124.


CORTICUS: Hydrocortisone in Septic CORTICUS: Hydrocortisone in Septic ShockShock

Question: Is low-dose hydrocortisone (HC) effective and safe in patients with septic shock?

Design: Rand, dbl-blind, HC vs placebo 499 pts w/ septic shock

Results: Hydrocort did not improve survival in any pts, faster shock reversal, incr adverse events

Conclusion: No indication for ACTH stim testComment: Prior study – sicker pts; hydrocort if

not responsive to fluids & vasopressors

CORTICUS. NEJM 2008;358:111-124.



Regarding the use of steroids in this patient with septic shock, you should:

A. Do a Cosyntropin (ACTH) stimulation test to see if she has a response.

B. Give hydrocortisone 50mg IV Q6o and fludrocortisone 50μg PO once daily.

C. Give hydrocortisone 50mg IV Q6o.

D. Topical hydrocortisone 1% to total body

E. Scratch it off the list (no steroids at this time).



The patient stabilizes in the ICU intubated on norepinephrine and antibiotics. Just as you’re leaving after a very long day, the nurse grabs you and says, “Hey, I just checked her blood sugar and it is 215mg/dL. Do you want to start an insulin drip?”


How should you respond to the nurse’s request regarding the insulin drip?

A. “I can’t believe I forgot – get the insulin drip going – our goal is to get her low: blood sugars of 80-110mg/dL.”

B. “Sure, start the drip but our goal is just to get her less than 150mg/dL.”

C. “Nah, just use the standard subcutaneous insulin protocol.”

D. “Blood sugar! Blood sugar! Hey, why don’t you come over here and check my blood sugar?!?”


Intensive Insulin in Severe Sepsis

Questions: Is intensive insulin therapy (goal bs 80-

110mg/dL) safe & effective in severe sepsis/shock?

Colloid v crystalloid in severe sepsis / shock?

Design: Multicenter, open-label, 2 x 2 factorial trialintensive v conventional (goal 180-

200mg/dL); LR v Pentastarch infusion

Brunkhorst FM. NEJM 2008;358:125-139.


ResultsResults

Intensive (bs

80-110mg/dL)

Conventional

(bs 180-200mg/dL)

Avg AM BS 112mg/dL 151mg/dL

28d Mortality

24.7% 26.0%

Hypoglycemia

17.0% 4.1%▪ Rates of life-threatening hypoglycemia higher in intensive group

▪ Pentastarch = BAD; Increased ARF, trend toward death.


Intensive Insulin in Septic ShockIntensive Insulin in Septic Shock

Questions: Is intensive insulin therapy (goal bs 80-110mg/dL) safe & effective in severe sepsis/shock?

Colloid v crystalloid in severe sepsis / shock?

Design: Rand, open-label, 2x2 factorial trialintensive v conven (goal 180-200mg/dL);LR v Pentastarch

Results: Intensive insulin w/ incr hypoglycemia

Pentastarch w/ serious side effectsConclusion: Intens insulin not indicated in sepsis in

MICU Do not use PentastarchComment: How intense is too intense?Brunkhorst FM. NEJM 2008;358:125-139..



How should you respond to the nurse’s request regarding the insulin drip?

A. “I can’t believe I forgot – get the insulin drip going – our goal is to get her low: blood sugars of 80-110mg/dL.”

B. “Sure, start the drip but our goal is just to get her less than 150mg/dL.”

C. “Nah, just use the standard subcutaneous insulin protocol.”

D. “Blood sugar! Blood sugar! Hey, why don’t you come over here and check my blood sugar?!?”



The patient does well (blood sugars remain near 150mg/dL) and is transferred out of the ICU 4 days later. On hospital day 7, she develops fever, abdominal pain, and diarrhea. She becomes tachycardic and mildly hypotensive, her wbc = 28,000 x103/mm3. You suspect severe Clostridium difficile infection.


What is the best therapy if this is severe C. difficile-associated diarrhea (CDAD)?

A. Metronidazole (Flagyl®) 250mg PO q6o

B. Vancomycin 125mg PO q6o

C. Metronidazole (Flagyl®) 250mg IV q6o

D. Yogurt. Lots of Yogurt.


Treatment of C. difficile

Questions: What is the most effective treatment for CDAD?

Does it depend on disease severity?Design: Rand, dbl-blind, placebo trial 150 pts w/ C.

diff; 81 mild, 69 severe; Metronidazole PO v vanco PO x10d

Zar FA. Clin Inf Dis. 2007;45:302-7.


ResultsResults

Vanco PO

Metro. PO

Overall cured

97% 84%*

Mild cured 98% 90%**

Severe cured

97% 76%** p < 0.05** p > 0.05

No difference in adverse events or relapse rates

Severe = ICU, colitis, age>60, fever, wbc>15, alb<2.5


Treatment of C. Treatment of C. difficledifficle

Question: What is the most effective tx for CDAD?Does it depend on disease severity?

Design:Rand, dbl-blnd, plac trial 150 pts w/ C. diff; 81 mild, 69 sev;

Metronidazole PO v vanco PO x10d

Results: Vanco = metronidazole for mild disease,

Vanco superior for severe CDADConclusion: Probably use vanco for severe CDADComment: But, not for mild – cost difference,

$6.60/pill vs. $0.11/pillZar FA. Clin Inf Dis. 2007;45:302-7.


What is the best therapy if this is severe C. difficile-associated diarrhea (CDAD)?

A. Metronidazole (Flagyl®) 250mg PO q6o

B. Vancomycin 125mg PO q6o

C. Metronidazole (Flagyl®) 250mg IV q6o

D. Yogurt. Lots of Yogurt.


SummarySummary

• Definitely1) Set goal BS of 150mg/dL in Medical ICU pts2) Treat severe CDAD with vancomycin PO

• Consider1) Using hydrocortisone in septic shock only in

patients refractory to fluids and vasopressors

• STOP1) Using vasopressin to treat septic shock2) Doing the ACTH stimulation test in septic

shock3) Using Pentastarch in septic shock



An 82 yo male with DM2, HTN, CAD presents with 5 hours of R sided upper extremity weakness & dysarthria. He noted palpitations but no other prodrome.

Vitals BP 170/85 HR 114 RR 12 Pox 94% RA. Expressive aphasia with 3/5 strength in the RUE and intact strength in the other extremities.

Head CT head shows no acute bleed.


A. The use of IV rTPA is indicated up to 3 hours after ischemic stroke onset.

B. The use of IV rTPA is indicated up to 6 hours after ischemic stroke onset.

C. The use of IV rTPA is indicated up to 12 hours after ischemic stroke onset.

D. IV rTPA is no longer indicated for acute ischemic stroke.

Which of the following is correct Which of the following is correct concerning recombinant tissue concerning recombinant tissue plasminogen activator?plasminogen activator?


SITS-MOSTSITS-MOST

Question: Is IV rTPA safe when given w/in 3 hrs of stroke onset in clinical practice across a wide range of sites?

Design: Prospective observational, 6483 pts, 14 countries, all given IV rTPA w/in 3 hours

SITS-MOST. Lancet 2007;369:275-282


ResultsResults

SITS-MOST Pooled RCTsIntracranial

hemorrhage 7 d

7.3% (6.7-7.9%)

8.6% (6.3-11.6%)

Death 3 mo 11.3% (10.5-12.1%)

17.3% (14.1-21.1%)

Independence 3 mo

54.8% (53.5-56%)

49% (44.4-53.6%)

Complete recovery 3 mo

38.9% (37.7-40.1%)

42.3% (37.8-47.0%)


SITS-MOSTSITS-MOST

Question: Is IV rTPA safe when given w/in 3 hours of stroke onset?

Design: Prospective observational, 6483 pts, 14 countries, all given IV rTPA w/in 3 hours

Results: ICH @ 7d 7.3% v. 8.6% Death @ 3 mo 11.3% v. 17.3%Independ @ 3 mo54.8% v. 49%Recovery @ 3 mo38.9% v. 42.3%

Conclusion: IV rTPA is safe and effective in routine use when used w/in 3 hours of presentation

Comment: Findings should encourage wider use of rTPA for suitable patients treated in stroke centers

SITS-MOST. Lancet 2007;369:275-282


A. The use of IV rTPA is indicated up to 3 hours after ischemic stroke onset.

B. The use of IV rTPA is indicated up to 6 hours after ischemic stroke onset.

C. The use of IV rTPA is indicated up to 12 hours after ischemic stroke onset.

D. IV rTPA is no longer indicated for acute ischemic stroke.

Which of the following is correct Which of the following is correct concerning recombinant tissue concerning recombinant tissue plasminogen activator?plasminogen activator?



The patient is outside the window of proven benefit for rTPA.

His aphasia improves but he still has weakness. He is otherwise asymptomatic. An EKG confirms the telemetry finding of atrial fibrillation.


In addition to aspirin therapy, which of the following is the next best step in his management?

A. UFH or LMWH at VTE prophylactic doses.

B. UFH at therapeutic doses.

C. LMWH at therapeutic doses.

D. Warfarin at therapeutic doses.


Efficacy & Safety of AC in Acute CVA

Question: What is the safety and efficacy of anticoagulation (AC) in the tx of

acute cardioembolic (CE) stroke?

Design: Meta-analysis of 7 RCTs, 4624 pt (3797 w/ AF)

-Objectively dx stroke of presumed cardioembolic origin

-Randomized w/in 48 hours from stroke onset -Compared full dose AC (UFH, LMWH,

Heparinoid) to ASA/placebo for initial therapy

Paciaroni M. Stroke 2007;38:423-430


Results

Event AC v. ASA/PlaceboOR (95% CI)

Death/Disability

1.01 (0.82-1.24)

All new stroke 1.18 (0.74-1.88)

PE 0.94 (0.44-2.00)

ICH 2.89 (1.19-7.01)Absolute increase in symptomatic ICH w/ AC was 1.8%

Number needed to harm for ICH w/ AC = 55


Efficacy & Safety of AC in Acute CVA

Question: What is the safety and efficacy of anticoagulation (AC) in the tx of acute

cardioembolic (CE) stroke? Design: Meta-analysis of 7 RCTs, 4624 pt (3797 w/ AF)

-Randomized w/in 48 hours from stroke onset -Objectively dx stroke of presumed cardioembolic origin

-Compared full dose AC (UFH, LWWH, Heparinoid) to ASA/placebo for initial therapy

Results:No ∆ death, CVA, PE. ↑ rate of ICH, NNH = 55Conclusion: AC for acute CE stroke does not improve

outcomes; associated with ↑rates of ICH Comment: Acute-AC not helpful. Chronic-AC

beneficial, optimal timing of starting AC still unclear.

Paciaroni M. Stroke 2007;38:423-430


In addition to aspirin therapy, which of the following is the next best step in his management?

A. UFH or LMWH at VTE prophylactic doses

B. UFH at therapeutic doses

C. LMWH at therapeutic doses

D. Warfarin at therapeutic doses


Short Take: Short Take: Safety of warfarin in patients > 75 Safety of warfarin in patients > 75 yoyo

• Prospective RCT of 973 pt > 75 yo w/ AFib showed warfarin use (INR 2-3) assoc. w/ 1-yr combined CVA, ICH, emboli rate of 1.8% compared to 3.8% w/ ASA (75mg) (RR 0.48, 0.28-0.80).

• Risk of extracranial bleed 1.4% v. 1.6% (RR 0.87, 0.43-1.73)Mant J. Lancet 2007;370:493-503


SummarySummary

• Definitely1) Prescribe rTPA w/in 3 hrs of acute ischemic

stroke.2) Use chronic warfarin AC in patients over the

age of 75 years with atrial fibrillation.

• STOP1) Giving therapeutic AC w/in 48 hrs of acute

ischemic stroke.



An 89 yo woman with DM2, HTN presents to ED c/o several hours of chest pressure and SOB.

Vitals: T36.8 BP 143/77 HR 102 RR: 16 97%/RAExam: thin, slightly diaphoretic woman, 2/6 SEMEKG: sinus tachycardiaLabs: troponin-I 2.9, Cr 1.5

She receives ASA, metoprolol, nitroglycerin and enoxaparin prescribed 60 mg subcutaneous twice daily.


A. Enoxaparin is an excellent choice because it is easy to dose and well tolerated.

B. Pt’s age increases her likelihood of complications from enoxaparin.

C. Pt’s renal function does not increase her likelihood of complications from enoxaparin.

D. Pt may have a higher risk of in-hospital mortality because of enoxaparin.

Which of the following is correct about Which of the following is correct about use of enoxaparin in non-ST elevation use of enoxaparin in non-ST elevation

MI (NSTEMI)?MI (NSTEMI)?


Enoxaparin Dosing Risk in Enoxaparin Dosing Risk in NSTEMINSTEMI

Question: In pts with NSTEMI, what is the relationship between enoxaparin dosing and outcomes?

Design: Observational study, from CRUSADE initiative, 10,687 pts, 332 hospitals

LaPointe NM. Arch Int Med 2007;167(14):1539-1544.

•Excess dose: >10mg/d above recommended dose•Under dose: <10mg/d below recommended dose•Rate of associated bleed or death


Results: Enoxaparin Dosing Results: Enoxaparin Dosing Risk in NSTEMIRisk in NSTEMI


Excess Dose

Recommend Dose

P value

Major bleeding

14.2% 7.3% <.001

Death 5.6% 2.4% <.001

•18.7% received excess dose•58% of patients w/ CrCl <30

•29.2% received under dose


Enoxaparin Dosing Risk in Enoxaparin Dosing Risk in NSTEMINSTEMI

Question: In pts with NSTEMI, what are the risks of dosing enoxaparin incorrectly?

Design: Observational study; 10,687 pts, 332 hospitalsResults: ~20% over dosed = ↑ risk major bleeding, death

~30% under dosed = trend toward ↑ deathConclusions: Nearly 50% of patients had the

wrong doseExcess enoxaparin dosing is common and harmful

Comment: Carefully estimate renal function1mg/kg daily for CrCl<30mL/min



A. Enoxaparin is an excellent choice because it is easy to dose and well tolerated.

B. Pt’s age does not increase her likelihood of complications from enoxaparin.

C. Pt’s renal function does not increase her likelihood of complications from enoxaparin.

Which of the following is correct about Which of the following is correct about use of enoxaparin in non-ST elevation use of enoxaparin in non-ST elevation MI (NSTEMI)?MI (NSTEMI)?

D. Pt may have a higher risk of in-hospital mortality because of enoxaparin.



The dose of the enoxaparin is adjusted later that day and she has no bleeding complications. At cardiac catheterization, there are multiple 60% lesions but none that require intervention and she is discharged on appropriate medical therapy.

Eighteen months later she is seen for worsening claudication and is scheduled for a femoral-popliteal bypass surgery. Your friend (a local primary care doctor) calls you about the case… “I know you took care of her before – does she need a stress test or a cath before surgery?”


A. Get a dobutamine echocardiogram and if it is positive, go to cath. If negative, proceed with surgery.

B. Go directly to cardiac catheterization because she is such high risk.

C. Maximize medical therapy and proceed with the vascular surgery.

D. Go do a cardiology fellowship.

You tell him that based on recent You tell him that based on recent studies, he should:studies, he should:


DECREASE-V: Revascularization before DECREASE-V: Revascularization before major vascular surgerymajor vascular surgery

Question: Is there a benefit to revascularization in the highest-risk pts getting major vascular surgery?

Design: Prospect, RCT of 101 high-risk pts & pos DSERevasc vs medical tx b/4 vascular surgery

DECREASE-V. J Am Coll Cardiol. 2007;49:1763-9.

High-risk ≥ 3 of: age > 70, angina, prior MI, CHF, DM, CKD, hx stroke


Results: DECREASE-VResults: DECREASE-V

• Medical treatment in 52 pts• Revascularization in 49 pts

• PCI in 32 pts, CABG in 17 pts• 75% of patients had either left main or 3 vv.

diseaseRevasc Medical

TxP

value

Death + MI, 30d

42.9% 32.7% 0.30

Death + MI, 1yr

49.9% 44.2% 0.48DECREASE-V. J Am Coll Cardiol. 2007;49:1763-9.


DECREASE-VDECREASE-V

Question: Is there a benefit to revascularization in the highest-risk pts getting major vasc surg?

Design: Prospect, RCT of 101 high-risk pts & pos DSERevasc vs medical tx b/4 vascular surgery

Results:Pre-op revasc in high-risk pts for major vasc surg did not improve outcome

Conclusion: Pt with significant ischemia do not benefit from prophylactic revasc prior to high risk surgery.

Comment: Study was pilot for larger 600 patient studySuggests preop revasc offers minimal benefit. Do not extrapolate findings to pts w/ USA.

DECREASE-V. J Am Coll Cardiol. 2007;49:1763-9.


A. Get a dobutamine echocardiogram and if it is positive, go to cath. If negative, proceed with surgery.

B. Go directly to cardiac catheterization because she is such high risk.

C. Maximize medical therapy and proceed with the vascular surgery.

D. Go do a cardiology fellowship.

You tell him that based on recent You tell him that based on recent studies, he should:studies, he should:



The patient goes to the OR and does well. One year later you have the chance to care for her again, this time co-managing her on the orthopedic service – while raking leaves she fell and fractured her hip.

She undergoes an uncomplicated R hip arthroplasty. On the day of discharge as you’re preparing the discharge medications, her husband asks some questions, including…


A. Sure, she can get some fancy hip protectors – those will work.

B. Two glasses of milk a day – does the body good.

C. She can get an intravenous medication once a year to protect her bones.

D. Calcium and vitamin D. E. Yeah, uh, don’t fall.

““Listen, Doc, is there anything we can Listen, Doc, is there anything we can do to keep her from breaking any bones do to keep her from breaking any bones in the future?” You answer:in the future?” You answer:


HORIZON: Zoledronic Acid after Hip HORIZON: Zoledronic Acid after Hip FractureFracture

Question: Does zoledronic acid reduce repeat fx and mortality after hip fracture?

Design: 2127 pts w/ hip fracture, within 90d p fxrandom to yearly zoledronic acid v placebo75% women, all vit D & Ca2+

Lyles KW. NEJM. 2007;357:1799-809.


Zoledronic Acid in Hip FxZoledronic Acid in Hip Fx

Zoledronic

Placebo p

Any Fracture 8.6% 13.9% 0.001

Mortality, 1yr 9.6% 13.3% 0.001

Lyles KW. NEJM. 2007;357:1799-809.

No difference in adverse events

NNT = 27


HORIZON: Zoledronic Acid after Hip HORIZON: Zoledronic Acid after Hip FractureFracture

Question: Does zoledronic acid reduce fx and mortality after hip fracture?

Design: Plac-cont, random 2127 pts w/ hip fracture zoledronic acid v placebo yearly;

Results: Zoledronic acid reduces fx and mort if given w/in 90days of hip fx

Conclusion: High mortality after hip fx: pts should get bisphosphonate + Ca/vit D

Comment: Consider prescription in hospital, include in discharge summary

Lyles KW. NEJM. 2007;357:1799-809.


A. Sure, she can get some fancy hip protectors – those will work.

B. Two glasses of milk a day – does the body good.

C. She can get an intravenous medication once a year to protect her bones.

D. Calcium and vitamin D. Done.E. Yeah, uh, don’t fall.

““Listen, Doc, is there anything we can Listen, Doc, is there anything we can do to keep her from breaking any bones do to keep her from breaking any bones in the future?” You answer:in the future?” You answer:


SummarySummary

• Definitely1) Give bisphosphonates to patients after hip

fracture.

• Consider1) Not revascularizing patients prior to surgery

unless unstable/would need anyway.

• STOP1) Giving inappropriate doses of enoxaparin in

ACS.


Case PresentationCase Presentation65 yo female smoker w/ DM2, CHF presents c/o fever,

sob & cough productive of rust-colored sputum.

T38.5 (101F) BP 143/77 HR 126 RR 20 93%RA

Diaphoretic, crackles at L base; CXR = LLL infiltrate Labs = normal except for BS 252 mg/dL

Pneumonia Severity Index (PSI) Score is 85 (class III)BCx drawn & first dose of antibiotics w/in 4 hrs Admitted to hospitalist service


A. Increased duration of antimicrobial therapy for CAP decreases antimicrobial resistance.

B. Duration of antimicrobial therapy has no impact on patient compliance.

C. The costs of therapy are similar, regardless of duration of antibiotic therapy for CAP.

D. Mild to mod CAP can be safely & effectively treated w/ an antibiotic regimen of </= 7 d

““Hey doc, does it matter how long I take the Hey doc, does it matter how long I take the antibiotics?” What’s your answer?antibiotics?” What’s your answer?


Duration of antibiotic therapy in Duration of antibiotic therapy in CAPCAP

Question: In pts with CAP, what is the appropriate duration of antibiotic therapy?

Design: Meta-analysis of 15 RCTs, 2796 adults (12 yrs or older) w/ mild to mod CAP

- short (</=7d) versus extended course regimens- excluded trials w/ large proportion of pts w/ bronchitis, COPD exacerb. or HCAP

Li JZ. Am J of Med 2007; 120(9):783-790.


ResultsResults

Risk of clinical failure

Short v. Extended course therapy

RR (95% CI)

All antibiotics 0.89 (0.78-1.02)

Macrolides 0.88 (0.71-1.09)

Fluoroquinolones 0.88 (0.71-1.08)

Beta lactams 0.92 (0.63-1.36)


Results: Duration of antibiotic Results: Duration of antibiotic therapy in CAPtherapy in CAP

Question: In pts with CAP, what is the appropriate duration of antibiotic therapy?

Design: Meta-analysis of 15 RCTs, 2796 adults (12 yrs or older) w/ mild to mod CAP

Results: No differences in clinical failure, adverse events or bacteriologic response b/w short & extended course therapy

Conclusion: Extended course antibiotic therapy (>7 days) does not improve clinical outcomes in mild to mod PNA

Comments: Elderly patients were under-represented; some antibiotics (e.g. doxycycline) were not evaluated; this trial only evaluated mild-mod pneumonia

Li JZ. Am J of Med 2007; 120(9):783-790.


A. Increased duration of antimicrobial therapy for CAP decreases antimicrobial resistance.

B. Duration of antimicrobial therapy has no impact on patient compliance.

C. The costs of therapy are similar, regardless of duration of antibiotic therapy for CAP.

D. Adults w/ mild to mod CAP can be safely & effectively treated w/ an antibiotic regimen of 7 days or less.

““Hey doc, does it matter how long I take the Hey doc, does it matter how long I take the antibiotics?” What’s your answer?antibiotics?” What’s your answer?


Short Take Short Take CAP: First dose of antibx w/in 4 CAP: First dose of antibx w/in 4 hrshrsQues: First dose antibx w/in 4h mandate….

Does it improve care?Design: Retro cohort; 107 (03) & 210 (05) ptsResults: Abx w/in 4 hrs: 66% (05) v 54% (03)

Bcxs before abx: 70% (05) v 47% (03) CAP dx/nl cxr: 29% (05) v 21% (03)Final dx CAP: 59% (05) v 76% (03)

Conclude: Inappropriate utilization of antibioticsComment: 6 hr window is more appropriate

Kanwar M. et al. Chest 2007; 161(6):1865-1869.


Case Presentation Case Presentation continuedcontinued

The patient is admitted to the hospitalist service. The nurse reminds you to order venous thromboembolism (VTE) prophylaxis for the patient.


A. UF heparin 5,000 units bid or tid offer similar risk reduction in prevention of VTE.

B. LMWH is assoc w/ higher risk of thrombocytopenia than UF heparin.

C. Neither UF heparin nor LMWH increases risk of major bleeding.

D. Both UF heparin and LMWH reduces DVT and PE in hospitalized medical patients.

““Any difference between unfractionated (UF) Any difference between unfractionated (UF) & low molecular wt heparin (LMWH) when & low molecular wt heparin (LMWH) when used for VTE prevention in medical pts?” used for VTE prevention in medical pts?”

What’s your answer?What’s your answer?


VTE prophylaxis in medical ptsVTE prophylaxis in medical pts

Question: Which agents most effectively prevent VTE in hospitalized medical patients?

Design: Meta-analysis of 36 prospective RCTs; Involved 48,000 patients

Wein L, et al. Arch Intern Med 2007 167(14) 1476-1486.


Results: VTE ProphylaxisResults: VTE Prophylaxis

• UFH v. Control•Reduced DVT/PE•No change in mortality

•Increase in bleeding•5,000 tid greater reduction in DVT compared to 5,000 bid

• LMWH v. Control•Reduced DVT/PE•No change in mortality•Increase in bleeding•No difference in thrombocytopenia


Results: LMWH vs UF Results: LMWH vs UF heparinheparin

Compared w/ UF heparin, LMWH assoc with… RR; 95% CI

●Reduced risk of DVT 0.68 (0.52-0.88)

●Reduce risk injxn site hematoma 0.47 (0.36-0.62)

●No diff in risk of total bleeds 0.83 (0.60-1.14)

●No diff in risk of PE 0.57 (0.25-1.34)

●No difference in mortality 1.16 (0.85-1.59)

●No diff in thrombocytopenia 0.25 (0.05-1.16)


VTE prophylaxis in medical ptsVTE prophylaxis in medical pts

Question: Which pharmacologic agents most effectively prevent VTE in hospitalized medical patients?

Design: Meta-analysis of 36 prospective RCTs ; Involved 48,000 patients

Conclusion: Both UF & LMWH reduce DVT & PE in hospitalized medical pts. Neither affect mortality. Both increase risk of major bleeding. LMWH, compared to all doses of UF heparin, was assoc w/ reduced risk of DVT; assoc w/ similar risk of PE

Wein L, et al. Arch Intern Med 2007 167(14) 1476-1486.


A. UF heparin 5,000 units bid or tid offer similar risk reduction in prevention of DVT

B. LMWH is assoc w/ higher risk of thrombocytopenia than UF heparin

C. Neither UF heparin or LMWH increases risk of major bleeding.

D. Both UF heparin and LMWH reduces DVT and PE in hospitalized medical patients.

““Any difference between unfractionated (UF) Any difference between unfractionated (UF) & low molecular wt heparin (LMWH) when & low molecular wt heparin (LMWH) when used for VTE prevention in medical pts?” used for VTE prevention in medical pts?”

What’s your answer?What’s your answer?


SummarySummary

• Definitely1) Prescribe either LMWH or UF hep tid for VTE

prophylaxis.

• Consider1) Giving antibiotics for 7 days or less for mild

to moderate CAP

• STOP1) Giving antibiotics to everyone just to

comply with the 4 hr antibiotic rule for CAP


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● Wein L, et al. Pharmacological Venous Thromboembolism Prophylaxis in Hospitalized Medical Patients. Arch Intern Med 2007; 167(4): 1476-1486.

● Johnstone J, et al. Effect of Pneumococcal Vaccination in Hospitalized Adults with Community-acquired Pneumonia. Arch Intern Med 2007; 167(18):1938-1943.

● Mohiuddin S, et al. Intensive Smoking Cessation Intervention Reduces Mortality in High Risk Smokers With Cardiovascular Disease. Chest 2007; 131(2):446-452.




• Hueb W. Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): A randomized clinical trial of three therapeutic strategies for multivessel coronary artery disease. Circ 2007;115:1082-1089.

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Thanks to fellow Thanks to fellow contributors!contributors!

• Mel Anderson, MDDenver VA Medical Center

• Anneliese Schleyer, MDWashington Harborview

• Brad Sharpe, MDUniv of California – San Francisco

Documents

Update in Hospital Medicine: Turning Evidence into Practice Joseph Li, MD Director, Hospital Medicine Beth Israel Deaconess Assistant Professor of Medicine