Inpatient Medicine: Year in Review Karen Hauer, MD UCSF August, 2006

Inpatient Medicine: Year in Review

Karen Hauer, MD

UCSF

August, 2006

Methods

• Literature review March 2005 - 2006• 11 major journals

Am J Med CirculationAnnals Internal Med Critical Care MedicineACP Journal Club JAMAArchives Internal Med LancetBMJ New Engl J MedicineCMAJ

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Selection criteria

• Relevance for inpatient medicine

• Potential to change, inform, or confirm practice

• Diverse topics, study types

Topics• Acute coronary syndromes• Insulin in the ICU• Clostridium difficile• Contrast nephropathy• PE• Diagnosing catheter-related infection• Medication discrepancies

Case

A 75 year old man with diabetes, hypertension, hyperlipidemia, dyspepsia on PPI, and COPD is admitted with chest pain, fever, and cough. Vital signs are pulse 95, BP 145/90, resp 22, 02 sat 97% on room air. On exam JVP is 9 cm, chest clear, cardiac RRR with S4, no edema. BNP is 250. ECG shows NSR with 2 mm ST elevation in V4-6. CXR shows LLL infiltrate.

Question #1

You administer aspirin 325 mg. Do you give Clopidogrel?

A. Yes, before percutaneous coronary intervention (PCI).

B. Yes, after PCIC. Yes, if tPA is givenD. No, aspirin is enough QuickTime™ and a

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Effect of Clopidogrel Pretreatment before PCI

• Negative consequences of platelet activation – Coronary artery thrombosis - plaque rupture– Thrombotic complications of percutaneous coronary

intervention (PCI)

• What is the optimal timing of clopidogrel treatment in patients with ST elevation MI (STEMI)?

– Initiated at time of PCI or – pretreatment


the PCI Clarity StudySabatine, N Engl J Med 2005;294:1224

• 1863 patients with recent STEMI• Randomized trial

– All patients received fibrinolytic, aspirin– Clopidogrel 300 mg load, then 75/day or placebo

• Initiated with fibrinolysis, then PCI at 2-8 days• Any patient getting stent received clopidogrel after

• Outcome: – Primary: composite of CV death, MI, or stroke from PCI to 30 days– Secondary: MI or stroke before PCI

Clopidogrel Pretreatment before PCI improved outcomes

Outcome Clopidogrel Pre-Rx

No pre-Rx

Adjusted odds ratio

p

CV death, MI, stroke post PCI

3.6% 6.2% 0.54 .008

MI or stroke

pre PCI

4.0% 6.2% 0.62 .03


the PCI Clarity Study• Clopidogrel pretreatment benefit

– Regardless of patient characteristics– For urgent/elective PCI regardless of timing

• No difference in bleeding– 2.0% vs. 1.9%– No increase in bleeding with clopidogrel

pretreatment plus GpIIb/IIIa inhibitor• Benefit of clopidogrel across a range of pretreatment

durations

Implications of Clopidogrel Pretreatment before PCI

• For every 100 patients undergoing PCI– Prevent 2 MI’s before PCI– Prevent 2 CV deaths, MI or stroke after PCI to 30

days• Addition of clopidogrel to ASA in 45,852 patients with

acute MI– 93% STEMI or BBB– 9% reduction in death, MI, or stroke at discharge

COMMIT. Lancet 2005;366:1607

Question #1

You administer aspirin 325 mg. Do you give Clopidogrel?

A. Yes, before percutaneous coronary intervention (PCI).



Topics• Acute coronary syndromes• Insulin in the ICU• Clostridium difficile• Contrast nephropathy• Pulmonary embolism• Diagnosing catheter-related infection• Medication discrepancies

CaseYour patient undergoes successful PCI

with stent placement. You also diagnosed pneumonia based on the presentation and initial CXR and started Levofloxacin. His oxygen requirements increase over the first 2 hospital days to the point that he is intubated and admitted to the ICU.

Question #2Do you initiate intensive insulin therapy in the

ICU?A. No, only in surgical ICU patients.B. Yes.C. Yes, if he is likely to be in the ICU for > 3

days.D. Yes, if glucose at ICU admission is > 300

mg/dl.

Intensive Insulin Therapy in the ICU

Van den Berghe, N Engl J Med 2001;345:1359

• Benefits of strict glucose control in surgical ICU– In-hospital mortality 11% vs. 7%, (p = .01)

• Greatest benefit with ICU stay > 3-5 days– Reduced morbidity

• Septicemia: 8% vs. 4% (p = .003)• Organ failure

• Does intensive insulin therapy improve prognosis in the medical ICU?

Intensive Insulin Therapy in the Medical ICU

Van den Berghe, N Engl J Med 2006;354:449 • Prospective, randomized, unblinded trial

– Intensive: insulin with goal glucose 80-110– Conventional treatment: insulin drip with goal

glucose 180-200• Primary outcome: in-hospital mortality

– Secondary outcomes: ICU mortality, organ failure, bacteremia or prolonged antibiotics

Intensive insulin therapy and in-hospital mortality

0

10

20

30

40

50

60

%

All patients ICU > 3 days

Conventional RxIntensive Rx

p = 0.33p = 0.009

Intensive insulin therapy and hypoglycemia

• Average glucose 150’s with conventional Rx vs. 100’s with intensive insulin

• More hypoglycemia with intensive insulin, but no adverse clinical events– Risk factors: ICU > 3 days, liver failure,

dialysis• Hypoglycemia was independent risk for

death

Intensive insulin therapy in the MICU: implications

• Mortality benefit for patients in ICU > 3 days similar to benefit in surgical ICU

• But. . . – Can’t predict length of ICU stay – Higher mortality with insulin & ICU < 3 days

• A reasonable approach – Aim for glucose <150 on ICU days 1-3– Consider goal of 80-110 after day 3

Question #2Do you initiate intensive insulin therapy in

the ICU?

C. Yes, if he is likely to be in the ICU for > 3 days.


Case: Question #3On hospital day 3, your patient has 4 loose

stools and subsequent stool testing reveals C. difficile colitis. What risk factors might explain his developing C. difficile infection?

A. Levofloxacin useB. PPI useC. Colonization with C. dif in the spore formD. Your washing your hands with an alcohol-based

hand sanitizer

The new Clostridium difficile: what does it mean?

• C diff colonization– 3% healthy adults– 20-40% hospitalized patients– Metabolically inactive spore form until gut flora perturbed

• C diff virulence factors: toxins A and B– 2 genes down-regulate toxin production– Binary toxin mediates potency of toxins A and B

Outbreaks of C diff in health care facilities

Loo VG. N Engl J Med 2005;353:2442.

• Prospective and case control studies of C diff outbreaks at 12 Quebec hospitals

• C diff: 2% of all admissions – 7% in patients > 90 years

• Mortality with C diff– 25% 30-day mortality – Attributable mortality 7%

• 14% in patients > 90 years

Case control study: risk factors for C diff

Exposure Odds ratio for C diff

Cephalosporins 3.8

Fluoroquinolones 3.9

Not associated with C diff:• Other antibiotics• Acid blockers, enteral feeding



Severe diarrhea associated with virulent strain

• Two genetic mutations increased virulence– Binary toxin gene– Partial deletion of suppressor gene

• Severe diarrhea: – 22/132 patients (17%) with mutations vs. 0/25 without

• All isolates susceptible to metronidazole, vancomycin

Implications:C diff may be evolving into a more severe disease

• 4X higher rate of C diff than in past years• Prevention and control

– Barrier precautions– Patient isolation– Cleaning environment with sporicidal agents– Handwashing - soap and water in addition to

alcohol-based sanitizers– Antibiotic restraint


are needed to see this p icture.

Gastric acid suppression and the risk of community-acquired C diff

Dial. JAMA. 2005;294:2989

• Case control study - United Kingdom population database– Not hospitalized in past year

• Factors associated with community-acquired C diff (adjusted risk)

– PPI: 2.9 – H2 blocker: 2.0– Only 37% had antibiotics in prior 90 dys

Case: Question #3On hospital day 3, your patient has 4 loose stools and

subsequent stool testing reveals C. difficile colitis. What risk factors might explain his developing C. difficile infection?

A. Levofloxacin useB. PPI useC. Colonization with C. dif in the spore formD. Your washing your hands with an alcohol-based hand sanitizer


Case: Question #4In the ICU, your patient develops worsening

hypoxia with stable infiltrates on chest x-ray. You suspect pulmonary embolism (PE), and you want to order a CT to evaluate. What is the best strategy to prevent contrast nephropathy?A. N-acetylcysteineB. BicarbonateC. IV hydration, & hope he doesn’t develop

CHFD. Hydrate, then lasix

Contrast Nephropathy

• Major causes of renal failure in the hospital– Prerenal, Medications– Contrast

• Consequences of contrast nephropathy– Prolonged hospitalization– Need for hemodialysis– Morbidity and mortality - especially with

cardiac disease

Oops, should have thought of this before the cardiac cath

Risk factors for Contrast Nephropathy

• Patient:

– Baseline renal insufficiency

– DM, CHF – Anemia– Hypertension,

hypotension– Age

• Contrast – Amount– Type



Contrast Nephropathy

• Definition– Creatinine increase by 25% or >= 0.5 mg/dl

within 48 hrs of contrast

• Incidence– 1.6-2.3% of all patients receiving contrast

• Pathophysiology – Vasoconstriction -> renal ischemia– Direct toxicity

Preventing Contrast Nephropathy: Meta-analysis of 59 trials

Pannu, JAMA 2006;295:2765

• Hydration– NS superior to half NS

• 1 ml/kg X 6-12 hrs pre-procedure, 6-12 hrs post

– D5W with 3 amps NaHCO3 better than NS before cardiac cath

• 3 ml/kg X 1 hr pre-procedure, 6 hrs post

– Oral hydration works, but IV probably betterMerten, JAMA. 2004;291:2328

Mueller, Arch Int Med. 2002;162:329

Preventing Contrast Nephropathy: What is the Evidence?

• N-acetylcysteine– Antioxidant– Dose: 600 mg BID X 2 days– Early evidence of dramatic benefit:

• 90% risk reduction vs. placebo (NEJM. 2000;343:180)

• Subsequent studies mostly favorable but less so

– Summary• Well-tolerated • May help

Preventing Contrast Nephropathy: Hemofiltration

Marenzi. NEJM 2003;349:1333

05

101520253035404550

Contrastnephropathy

In-hospitalmortality

Hemofiltration Hydration alone

%

Preventing Contrast Nephropathy: Summary of the Evidence

• Yes– Identify high-risk

patients– Avoid

unnecessary contrast

– Hydration

• No– Hemodialysis– Fenoldopam– Dopamine– Diuretics

• Maybe– Hemofiltration– Acetylcysteine – Theophylline

Summary Recommendations

>= 2 risk factors for contrast nephropathy

IV hydration before procedureConsider N-acetylcysteine

Iso or low-osmolar contrast, minimize amount

IV hydration after procedure

Case: Question #4What is the best strategy to prevent

contrast nephropathy?

Risk factors for contrast nephropathy? yes

C. IV hydration





hypoxia with stable infiltrates on chest x-ray. You suspect pulmonary embolism (PE), but a chest CT is negative for PE. What do you do next?A. D-dimerB. LE doppler ultrasoundC. Pulmonary angiographyD. Conclude that PE is ruled out

Diagnostic tests for PE in the hospital

• D-dimer: unhelpful – low specificity in hospitalized or post-op patients, or

with cancer

• Ultrasound: specificity > sensitivity– 40% with DVT may have asymptomatic PE

• Angiography: gold standard, invasive• CT: sensitivity for central PE high

– What about subsegmental PE’s? • Sensitivity may be as low as 29% - significance?

Clinical Validity of a Negative CT with suspected PE: a systematic review

Quiroz. JAMA. 2005;293:2012.

• Meta-analysis of 15 studies using CT to rule out PE– 3500 patients, 7 nations– Patient follow up 3-12 months

• After negative CT: – Negative likelihood ratio of clot = 0.07– Negative predictive value: 99.1%– No benefit to additional studies prior to CT

Clinical Validity of a Negative CT with suspected PE? Yes!

• Negative predictive value of CT (99%) compares favorably to:– V/Q scan: 76-88%– Pulmonary angiography: 98-100%

• Visualization of peripheral pulmonary arteries

– improving with better CT techniques

• A negative chest CT rules out PE– No further testing needed


hypoxia with stable infiltrates on chest x-ray. You suspect pulmonary embolism (PE), but a chest CT is negative for PE. What do you do next?

D. Conclude that PE is ruled out


Case

Your patient spikes a temperature to 39 degrees. On exam BP is 140/80, heart rate 100. He has no localizing findings. He has a clean internal jugular line site but you are still concerned about central line infection. How do you make this diagnosis?

Question #5

A.Remove the catheter, culture the tipB.Draw blood cultures peripheral and

through the catheterC.Draw 2 peripheral blood culturesD.Any diagnostic approach is fine as long

as I don’t need to replace the central line



Catheter-related bloodstream infection

• High morbidity and mortality– 12-27% mortality– Prolong hospital stay by 1 week

• Clinical presentation - nonspecific– Fever, +/- hypotension– No other source– Line site usually clean– Increased risk with catheter > 7 days



Diagnosing intravascular device-related bloodstream infection

• Remove the catheter– Qualitative or quantitative tip culture

• or. . . . Keep the catheter– Blood cultures through the catheter– Catheter and peripheral blood cultures

• Differential time to positivity > 2 hours• Paired quantitative cultures: 3-5 X higher

concentration of organisms from catheter

Meta-analysis: Methods of diagnosing intravascular device-

related bloodstream infectionSafdar. Ann Intern Med. 2005;142;451.

• Highest sensitivity– Qualitative cultures: catheter tip (90%) or through

catheter (87%)– Paired quantitative blood cultures (87%)– Differential time to positivity (85%)

• Highest specificity– Paired quantitative blood cultures (98%)– Quantitative blood culture through catheter (90%)

Summary: diagnostic tests for catheter-related bloodstream

infection• Best test: Paired quantitative blood cultures

–Differential time to positivity also accurate and more widely available

• Only test when catheter infection suspected–Positive predictive value of tests much

higher with high clinical suspicion–Avoids overuse of antibiotics

Question #5

B. Draw blood cultures peripheral and through the catheter




CaseUnder your excellent care, your patient is ready

to return home from the hospital. His medications on discharge are coumadin, atenolol, benazepril, atorvastatin, and omeprazole.

As you handoff his care to his primary care doctor, what are the risks of a medication problem?



Question #6A.None - you explained the regimen to him

yourselfB.He has close primary care followup so he

should be fine until his clinic appointmentC.You are fine because of your system to meet

the JHACO Patient Safety Goal to obtain and document the patient’s medications on admission, and discharge

D.The risk is real and a medication discrepancy would increase his risk of readmission

JHACO National Patient Safety Goal #8: medication reconciliation

• Medication reconciliation – process during a transition in care – comparing what medications the patient has been

taking previously with the medications about to be provided

• Hospital admission and discharge: important transitions in care

– Discharge medication list must be communicated to the next provider of care (not just the patient)

Post Hospital Medication DiscrepanciesColeman. Arch Intern Med. 2005;165:1842.

• What are the prevalence and contributing factors associated with medication discrepancies -

– prehospital -> discharge -> meds actually taken after discharge

• What are risk factors for medication discrepancies?• Are medication discrepancies associated with

readmission?

Post Hospital Medication Discrepancies: study population

• 375 Adults >= 65 years old• Admitted with common conditions likely to require

discharge to skilled nursing facility– CHF, COPD, CAD, DM, stroke, PVD, arrhythmia– Back conditions, hip fracture

• Discrepancies = what was patient told vs. what was planned

Categorizing Medication Discrepancies

• Medication Discrepancy Tool (MDT)– Meds assessed by NP 24-72 hours after

discharge to home • Discrepancies

– Systems-based: doctor or system– Patient-based: intentional or non-intentional

• Did they try to take it correctly?

Medication Discrepancies

• 14% of patients– 38% of those had > 1 discrepancy

• Average # meds: 9 with discrepancy vs. 7 without (p < .001)

• Common offenders (50% of discrepancies)– Anticoagulants– Diuretics, ACE inhibitors– Lipid-lowering agents– PPIs



Causes of Medication Discrepancies

Patient (51%)• Nonintentional

nonadherence (34%)• $$ • Intentional

nonadherence

System (49%)• Bad instructions• Conflicting

instructions• Duplication





Implications of Medication Discrepancies

• 30-day readmission rates higher with medication discrepancies (14% vs. 6%, p =.04)

• Transitions of care are a high risk time– Medication reconciliation in the hospital won’t

solve the problem– Multiple interventions needed

• Post discharge follow up reconciliation• Systems improvements• Patient education

Question #6

D. The risk is real and a medication discrepancy would increase his risk of readmission

Take Home Points

• Acute coronary syndromes: clopidogrel plus ASA before PCI improves outcomes

• Insulin in the medical ICU: tight glucose control improves survival with ICU stay > 3 days

• Clostridium difficile: increasingly virulent, increasingly common in the hospital and community

Take Home Points

• Contrast nephropathy: IV hydration for high risk patients

• PE: negative spiral CT rules out clinically important PE

• Diagnosing catheter-related infection: diagnose with paired catheter and peripheral quantitative cultures, or differential time to positivity

• Medication discrepancies: common after hospital discharge due to nonintentional non-adherence or systems problems

Documents

Inpatient Medicine: Year in Review Karen Hauer, MD UCSF August, 2006