Inpatient Medicine: Year in Review

1
Inpatient Medicine Year in Review

• Karen Hauer, MD
• UCSF
• August, 2006

2
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

3
Selection criteria

• Relevance for inpatient medicine
• Potential to change, inform, or confirm practice
• Diverse topics, study types

4
Topics

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

5
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.

6
Question 1

• You administer aspirin 325 mg. Do you give
  Clopidogrel?
• Yes, before percutaneous coronary intervention
  (PCI).
• Yes, after PCI
• Yes, if tPA is given
• No, aspirin is enough

7
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

8
Effect of Clopidogrel Pretreatment before PCIthe
PCI Clarity StudySabatine, N Engl J Med
20052941224

• 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

9
Clopidogrel Pretreatment before PCI improved
outcomes
10
Effect of Clopidogrel Pretreatment before PCIthe
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

11
Implications of Clopidogrel Pretreatment before
PCI

• For every 100 patients undergoing PCI
• Prevent 2 MIs 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 20053661607

12
Question 1

• You administer aspirin 325 mg. Do you give
  Clopidogrel?
• Yes, before percutaneous coronary intervention
  (PCI).

13
Topics

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

14
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.

15
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 gt 3
  days.
• D. Yes, if glucose at ICU admission is gt 300
  mg/dl.

16
Intensive Insulin Therapy in the ICU Van den
Berghe, N Engl J Med 20013451359

• Benefits of strict glucose control in surgical
  ICU
• In-hospital mortality 11 vs. 7, (p .01)
• Greatest benefit with ICU stay gt 3-5 days
• Reduced morbidity
• Septicemia 8 vs. 4 (p .003)
• Organ failure
• Does intensive insulin therapy improve prognosis
  in the medical ICU?

17
Intensive Insulin Therapy in the Medical ICU Van
den Berghe, N Engl J Med 2006354449

• 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

18
Intensive insulin therapy and in-hospital
mortality
p 0.009
p 0.33
19
Intensive insulin therapy and hypoglycemia

• Average glucose 150s with conventional Rx vs.
  100s with intensive insulin
• More hypoglycemia with intensive insulin, but no
  adverse clinical events
• Risk factors ICU gt 3 days, liver failure,
  dialysis
• Hypoglycemia was independent risk for death

20
Intensive insulin therapy in the MICU
implications

• Mortality benefit for patients in ICU gt 3 days
  similar to benefit in surgical ICU
• But. . .
• Cant predict length of ICU stay
• Higher mortality with insulin ICU lt 3 days
• A reasonable approach
• Aim for glucose lt150 on ICU days 1-3
• Consider goal of 80-110 after day 3

21
Question 2

• Do you initiate intensive insulin therapy in the
  ICU?
• C. Yes, if he is likely to be in the ICU for gt 3
  days.

22
Topics

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

23
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?
• Levofloxacin use
• PPI use
• Colonization with C. dif in the spore form
• Your washing your hands with an alcohol-based
  hand sanitizer

24
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

25
Outbreaks of C diff in health care facilitiesLoo
VG. N Engl J Med 20053532442.

• Prospective and case control studies of C diff
  outbreaks at 12 Quebec hospitals
• C diff 2 of all admissions
• 7 in patients gt 90 years
• Mortality with C diff
• 25 30-day mortality
• Attributable mortality 7
• 14 in patients gt 90 years

26
Case control study risk factors for C diff

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

27
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

28
ImplicationsC 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

29
Gastric acid suppression and the risk of
community-acquired C diff Dial. JAMA.
20052942989

• 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

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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?
• Levofloxacin use
• PPI use
• Colonization with C. dif in the spore form
• Your washing your hands with an alcohol-based
  hand sanitizer

31
Topics

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

32
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 doesnt develop CHF
• D. Hydrate, then lasix

33
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

34
Risk factors for Contrast Nephropathy

• Patient
• Baseline renal insufficiency
• DM, CHF
• Anemia
• Hypertension, hypotension
• Age

• Contrast
• Amount
• Type

35
Contrast Nephropathy

• Definition
• Creatinine increase by 25 or gt 0.5 mg/dl within
  48 hrs of contrast
• Incidence
• 1.6-2.3 of all patients receiving contrast
• Pathophysiology
• Vasoconstriction -gt renal ischemia
• Direct toxicity

36
Preventing Contrast Nephropathy Meta-analysis
of 59 trialsPannu, JAMA 20062952765

• 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. 20042912328
• Mueller, Arch Int Med. 2002162329

37
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. 2000343180)
• Subsequent studies mostly favorable but less so
• Summary
• Well-tolerated
• May help

38
Preventing Contrast Nephropathy Hemofiltration

• Marenzi. NEJM 20033491333

39
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

40
Summary Recommendations

• gt 2 risk factors for contrast nephropathy
• IV hydration before procedure
• Consider N-acetylcysteine
• Iso or low-osmolar contrast, minimize amount
• IV hydration after procedure

41
Case Question 4

• What is the best strategy to prevent contrast
  nephropathy?
• Risk factors for contrast nephropathy? yes
• C. IV hydration

42
Topics

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

43
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

44
Diagnostic tests for PE in the hospital

• D-dimer unhelpful
• low specificity in hospitalized or post-op
  patients, or with cancer
• Ultrasound specificity gt sensitivity
• 40 with DVT may have asymptomatic PE
• Angiography gold standard, invasive
• CT sensitivity for central PE high
• What about subsegmental PEs?
• Sensitivity may be as low as 29 - significance?

45
Clinical Validity of a Negative CT with suspected
PE a systematic reviewQuiroz. JAMA.
20052932012.

• 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

46
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

47
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

48
Topics

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

49
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?

50
Question 5

• Remove the catheter, culture the tip
• Draw blood cultures peripheral and through the
  catheter
• Draw 2 peripheral blood cultures
• Any diagnostic approach is fine as long as I
  dont need to replace the central line

51
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 gt 7 days

52
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 gt 2 hours
• Paired quantitative cultures 3-5 X higher
  concentration of organisms from catheter

53
Meta-analysis Methods of diagnosing
intravascular device-related bloodstream
infectionSafdar. Ann Intern Med. 2005142451.

• 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)

54
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

55
Question 5

• B. Draw blood cultures peripheral and through the
  catheter

56
Topics

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

57
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?

58
Question 6

• None - you explained the regimen to him yourself
• He has close primary care followup so he should
  be fine until his clinic appointment
• You are fine because of your system to meet the
  JHACO Patient Safety Goal to obtain and document
  the patients medications on admission, and
  discharge
• The risk is real and a medication discrepancy
  would increase his risk of readmission

59
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)

60
Post Hospital Medication DiscrepanciesColeman.
Arch Intern Med. 20051651842.

• What are the prevalence and contributing factors
  associated with medication discrepancies -
• prehospital -gt discharge -gt meds actually taken
  after discharge
• What are risk factors for medication
  discrepancies?
• Are medication discrepancies associated with
  readmission?

61
Post Hospital Medication Discrepancies study
population

• 375 Adults gt 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

62
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?

63
Medication Discrepancies

• 14 of patients
• 38 of those had gt 1 discrepancy
• Average meds 9 with discrepancy vs. 7 without
  (p lt .001)
• Common offenders (50 of discrepancies)
• Anticoagulants
• Diuretics, ACE inhibitors
• Lipid-lowering agents
• PPIs

64
Causes of Medication Discrepancies

• System (49)
• Bad instructions
• Conflicting instructions
• Duplication

• Patient (51)
• Nonintentional nonadherence (34)
• Intentional nonadherence

65
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 wont
  solve the problem
• Multiple interventions needed
• Post discharge follow up reconciliation
• Systems improvements
• Patient education

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Question 6

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

67
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 gt 3 days
• Clostridium difficile increasingly virulent,
  increasingly common in the hospital and community

68
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