Transcript Inpatient Medicine: Year in Review

Inpatient Medicine:
Year in Review
Karen Hauer, MD
UCSF
August, 2006
Qu ickT ime™ an d a
TIF F (U ncom pre ssed ) dec omp ress or
are nee ded to se e thi s pic ture .
Methods
• Literature review March 2005 - 2006
• 11 major journals
Am J Med
Circulation
Annals Internal Med Critical Care Medicine
ACP Journal Club
JAMA
Archives Internal Med
Lancet
BMJ
New Engl J Medicine
CMAJ
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 PCI
C. Yes, if tPA is given
Quic kT ime™ and a
D. No, aspirin is enough
T IFF (Uncompress ed) decompress or
are needed to s ee this pi cture.
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
Effect of Clopidogrel
Pretreatment before PCI
the PCI Clarity Study
Sabatine, 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 No pre- Adjusted
Pre-Rx
Rx
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
Effect of Clopidogrel
Pretreatment before PCI
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).
Quic kT ime™ and a
T IFF (Uncompress ed) decompress or
are needed to s ee this pi cture.
Topics
•
•
•
•
•
•
•
Acute coronary syndromes
Insulin in the ICU
Clostridium difficile
Contrast nephropathy
Pulmonary embolism
Diagnosing catheter-related infection
Medication discrepancies
Case
Your 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 #2
Do 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
ar e n eed ed to see thi s p ictu re.
TIFF (Un co mp res sed ) d eco mp re sso r
Quic kTime™ a nd a
Intensive insulin therapy and
in-hospital mortality
60
50
40
p = 0.009
p = 0.33
% 30
Conventional Rx
Intensive Rx
20
10
0
All patients
ICU > 3 days
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 #2
Do you initiate intensive insulin therapy in
the ICU?
C. Yes, if he is likely to be in the ICU for >
3 days.
Topics
•
•
•
•
•
•
•
Acute coronary syndromes
Insulin in the ICU
Clostridium difficile
Contrast nephropathy
Pulmonary embolism
Diagnosing catheter-related infection
Medication discrepancies
Case: Question #3
On 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.
B.
C.
D.
Levofloxacin use
PPI use
Colonization with C. dif in the spore form
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
Quick Time™ a nd a
TIFF ( Un compr ess ed ) d eco mp res so r
ar e n eed ed to s ee this pi ctur e.
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
Qu ickT ime™ an d a
TIF F (U ncom pres sed) deco mpr esso r
are nee ded t o se e this pict ure.
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 #3
On 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.
B.
C.
D.
Levofloxacin use
PPI use
Colonization with C. dif in the spore form
Your washing your hands with an alcohol-based hand sanitizer
Topics
•
•
•
•
•
•
•
Acute coronary syndromes
Insulin in the ICU
Clostridium difficile
Contrast nephropathy
Pulmonary embolism
Diagnosing catheter-related infection
Medication discrepancies
Case: Question #4
In 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-acetylcysteine
B. Bicarbonate
C. IV hydration, & hope he doesn’t develop
CHF
D. 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
QuickTime™ and a
TIFF(U ncompres sed) dec ompressor
are needed to see thi s pic ture.
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 better
Merten, 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
Hemofiltration
%
Hydration alone
50
45
40
35
30
25
20
15
10
5
0
Contrast
nephropathy
In-hospital
mortality
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 procedure
Consider N-acetylcysteine
Iso or low-osmolar contrast, minimize
amount
IV hydration after procedure
Case: Question #4
What is the best strategy to prevent
contrast nephropathy?
Risk factors for contrast nephropathy?
yes
C. IV hydration
Topics
•
•
•
•
•
•
•
Acute coronary syndromes
Insulin in the ICU
Clostridium difficile
Contrast nephropathy
Pulmonary embolism
Diagnosing catheter-related infection
Medication discrepancies
Quic kTi me™ a nd a
TIFF (Un co mp res se d) d ec ompre ss or
ar e n ee ded to see th is p ictu re .
Case: Question #4
In the ICU, your patient develops worsening
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-dimer
B. LE doppler ultrasound
C. Pulmonary angiography
D. 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
Case: Question #4
In the ICU, your patient develops worsening
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
Topics
•
•
•
•
•
•
•
Acute coronary syndromes
Insulin in the ICU
Clostridium difficile
Contrast nephropathy
Pulmonary embolism
Diagnosing catheter-related infection
Medication discrepancies
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 tip
B.Draw blood cultures peripheral and
through the catheter
C.Draw 2 peripheral blood cultures
D.Any diagnostic approach is fine as long
as I don’t need to replace the central
line
Quick Time™ a nd a
TIFF ( Un compr ess ed ) de co mp res sor
ar e n eed ed to s ee this pic tur e.
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
Quic kTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this pictu re.
Diagnosing intravascular devicerelated 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 devicerelated bloodstream infection
Safdar. 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
Quick Time™ a nd a
TIFF ( Un compr ess ed ) de co mp res sor
ar e n eed ed to s ee this pic tur e.
Topics
•
•
•
•
•
•
•
Acute coronary syndromes
Insulin in the ICU
Clostridium difficile
Contrast nephropathy
Pulmonary embolism
Diagnosing catheter-related infection
Medication discrepancies
Case
Under 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?
QuickTime™ and a
TIFF(U ncompres sed) dec ompressor
are needed t o see this pic ture.
Question #6
A.None - you explained the regimen to him
yourself
B.He has close primary care followup so he
should be fine until his clinic appointment
C.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 Discrepancies
Coleman. 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
Qu ickT ime™ an d a
TIF F (U ncom pre ssed ) de com press or
are nee ded to se e th is pi cture .
Causes of Medication Discrepancies
Patient (51%)
System (49%)
• Nonintentional
nonadherence (34%)
• $$
• Intentional
nonadherence
• Bad instructions
• Conflicting
instructions
• Duplication
Qu ickT ime ™ a nd a
TIF F (U nco mpre sse d) de com pres sor
are nee ded to s ee th is pi cture .
Quic kT ime™ and a
T IFF (Uncompress ed) dec ompress or
are needed to s ee this pic ture.
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 nonadherence or systems problems