Presentation on theme: "Inpatient Medicine: Year in Review"— Presentation transcript:
1 Inpatient Medicine: Year in Review Karen Hauer, MDUCSFAugust, 2006
2 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
3 Selection criteria Relevance for inpatient medicine Potential to change, inform, or confirm practiceDiverse topics, study types
4 Topics Acute coronary syndromes Insulin in the ICU Clostridium difficileContrast nephropathyPEDiagnosing catheter-related infectionMedication discrepancies
5 CaseA 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 PCIYes, if tPA is givenNo, aspirin is enough
7 Effect of Clopidogrel Pretreatment before PCI Negative consequences of platelet activationCoronary artery thrombosis - plaque ruptureThrombotic 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 orpretreatment
8 Effect of Clopidogrel Pretreatment before PCI the PCI Clarity Study Sabatine, N Engl J Med 2005;294:12241863 patients with recent STEMIRandomized trialAll patients received fibrinolytic, aspirinClopidogrel 300 mg load, then 75/day or placeboInitiated with fibrinolysis, then PCI at 2-8 daysAny patient getting stent received clopidogrel afterOutcome:Primary: composite of CV death, MI, or stroke from PCI to 30 daysSecondary: MI or stroke before PCIWithout load, it takes approx 3-5 days for the antiplt effects of clopidogrel to reach steady state; w/ load, it takes only several hours
9 Clopidogrel Pretreatment before PCI improved outcomes Clopidogrel Pre-RxNo pre-RxAdjusted odds ratiopCV death, MI, stroke post PCI3.6%6.2%0.54.008MI or strokepre PCI4.0%0.62.03Outcome post PCI: NNT = 39Trend toward benefit for CV death, MI, stroke individually altho none statistically significantSeparated soon after PCI and continued to diverge over timeCombining benefits pre and post PCI NNT = 23
10 Effect of Clopidogrel Pretreatment before PCI the PCI Clarity Study Clopidogrel pretreatment benefitRegardless of patient characteristicsFor urgent/elective PCI regardless of timingNo difference in bleeding2.0% vs. 1.9%No increase in bleeding with clopidogrel pretreatment plus GpIIb/IIIa inhibitorBenefit of clopidogrel across a range of pretreatment durationsBleeding - 2% includes major and minor bleeding
11 Implications of Clopidogrel Pretreatment before PCI For every 100 patients undergoing PCIPrevent 2 MI’s before PCIPrevent 2 CV deaths, MI or stroke after PCI to 30 daysAddition of clopidogrel to ASA in 45,852 patients with acute MI93% STEMI or BBB9% reduction in death, MI, or stroke at dischargeCOMMIT. Lancet 2005;366:1607COMMIT-half pts received fibrinolytics (urokinase), 5% underwent angiographyBenefit of clopidogrel emerged at day 1 despite no loadtakenTaken together, these 2 studies demonstrate benefit of clopidogrel for STEMI
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 difficileContrast nephropathyPulmonary embolismDiagnosing catheter-related infectionMedication discrepancies
14 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.
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 > 3 days.D. Yes, if glucose at ICU admission is > 300 mg/dl.
16 Intensive Insulin Therapy in the ICU Van den Berghe, N Engl J Med 2001;345:1359 Benefits of strict glucose control in surgical ICUIn-hospital mortality 11% vs. 7%, (p = .01)Greatest benefit with ICU stay > 3-5 daysReduced morbiditySepticemia: 8% vs. 4% (p = .003)Organ failureDoes intensive insulin therapy improve prognosis in the medical ICU?Hyperglycemia and insulin resistance are common in the ICU2001 single institution study in Belgium, 2/3 post cardiac surgeryUsual care: maintain glucose , vs (fed on ICU d2); check gluc q 4 hra.m. gluc avg’s 150 vs. 103Primary outcome = death during intensive care. Effect was independent of h/o DMNo mortality benefit in first 5 daysCriticisms: single institution, not blinded, high mortality rate for surgical pts, all pt’s fed
17 Intensive Insulin Therapy in the Medical ICU Van den Berghe, N Engl J Med 2006;354:449 Prospective, randomized, unblinded trialIntensive: insulin with goal glucoseConventional treatment: insulin drip with goal glucosePrimary outcome: in-hospital mortalitySecondary outcomes: ICU mortality, organ failure, bacteremia or prolonged antibioticsRole of insulin in MICU has been unknown; patients are sicker than in SICUPatients: expected to need ICU for >= 3 days; enteral feeding as soon as stable17% had DMConventional group: start insulin when gluc > 215, taper insulin when gluc < 180Enteral feeding started as soon as possible after pts hemodynamically stableOther 2ndary outcomes: LOS in ICU and hosp, new renal failure
18 Intensive insulin therapy and in-hospital mortality All patients: 40% vs. 37% ; if >= 3 days was 53% vs. 43%3 days NNT = 10Predefined subgroup of patients staying in ICU at least 3 days. Excluded patients waiting for floor bed (taking > 2/3 diet p.o., no vital organ support)Small benefits for: creatinine; earlier weaning, earlier discharge from ICU and hosp. no change in infection.Reduced the risk of creatinine elevation, but not need for HD
19 Intensive insulin therapy and hypoglycemia Average glucose 150’s with conventional Rx vs. 100’s with intensive insulinMore hypoglycemia with intensive insulin, but no adverse clinical eventsRisk factors: ICU > 3 days, liver failure, dialysisHypoglycemia was independent risk for deathHypoglycemia = < 40Hypoglycemia no hemodynamic instability or Sz, most pt’s only had one episodeLiver failure = transaminase > 250Mortality = in-hospital
20 Intensive insulin therapy in the MICU: implications Mortality benefit for patients in ICU > 3 days similar to benefit in surgical ICUBut. . .Can’t predict length of ICU stayHigher mortality with insulin & ICU < 3 daysA reasonable approachAim for glucose <150 on ICU days 1-3Consider goal of after day 3Short ICU stay - may have been due to withdrawal of support, vs hyperglycemia may be adaptive early on in ICU, or insulin may cause stressMaybe early inc gluc is adaptive, or insulin is a metabolic stressor; some can’t respond w/ catecholsA reasonable approach while we await more data. Good to avoid marked hyperglycemia.After day 3 - you have started feeds, which would protect agnst hypoglycemia.
21 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.
22 Topics Acute coronary syndromes Insulin in the ICU Clostridium difficileContrast nephropathyPulmonary embolismDiagnosing catheter-related infectionMedication discrepancies
23 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?Levofloxacin usePPI useColonization with C. dif in the spore formYour washing your hands with an alcohol-based hand sanitizer
24 The new Clostridium difficile: what does it mean? C diff colonization3% healthy adults20-40% hospitalized patientsMetabolically inactive spore form until gut flora perturbedC diff virulence factors: toxins A and B2 genes down-regulate toxin productionBinary toxin mediates potency of toxins A and BOld pathogen that is emerging with increased virulence.Then converts to vegetative form that replicates, produces toxin
25 Outbreaks of C diff in health care facilities Loo VG 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 hospitalsC diff: 2% of all admissions7% in patients > 90 yearsMortality with C diff25% 30-day mortalityAttributable mortality 7%14% in patients > 90 years1700 patients in an epidemic at 12 hospitals over 5.5 monthsIncidence, mortality due to C diff increased with patient age
26 Case control study: risk factors for C diff ExposureOdds ratio for C diffCephalosporins3.8Fluoroquinolones3.9Not associated with C diff:Other antibioticsAcid blockers, enteral feeding
27 Severe diarrhea associated with virulent strain Two genetic mutations increased virulenceBinary toxin genePartial deletion of suppressor geneSevere diarrhea:22/132 patients (17%) with mutations vs. 0/25 withoutAll isolates susceptible to metronidazole, vancomycinMore virulent strain based on genetic analysis - 84% of cases analyzed had these 2 mutationsRESISTANT to quinolones
28 Implications:C diff may be evolving into a more severe disease 4X higher rate of C diff than in past yearsPrevention and controlBarrier precautionsPatient isolationCleaning environment with sporicidal agentsHandwashing - soap and water in addition to alcohol-based sanitizersAntibiotic restraintLook for epidemic strainTherefore focus on control, and early ID of outbreaks
29 Gastric acid suppression and the risk of community-acquired C diff Dial. JAMA. 2005;294:2989 Case control study - United Kingdom population databaseNot hospitalized in past yearFactors associated with community-acquired C diff (adjusted risk)PPI:H2 blocker: 2.0Only 37% had antibiotics in prior 90 dysMost labs won’t test for the epidemic strain, but it can be suspected based on incidence and severity of disease
30 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?Levofloxacin usePPI useColonization with C. dif in the spore formYour washing your hands with an alcohol-based hand sanitizer
31 Topics Acute coronary syndromes Insulin in the ICU Clostridium difficileContrast nephropathyPulmonary embolismDiagnosing catheter-related infectionMedication discrepancies
32 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
33 Contrast Nephropathy Major causes of renal failure in the hospital Prerenal, MedicationsContrastConsequences of contrast nephropathyProlonged hospitalizationNeed for hemodialysisMorbidity and mortality - especially with cardiac diseaseOops, should have thought of thisbefore the cardiac cathAfter cardiac cath, pt’s with ARF have 20% mortality rate
35 Contrast Nephropathy Definition Incidence Pathophysiology Creatinine increase by 25% or >= 0.5 mg/dl within 48 hrs of contrastIncidence% of all patients receiving contrastPathophysiologyVasoconstriction -> renal ischemiaDirect toxicity
36 Preventing Contrast Nephropathy: Meta-analysis of 59 trials Pannu, JAMA 2006;295:2765 HydrationNS superior to half NS1 ml/kg X 6-12 hrs pre-procedure, 6-12 hrs postD5W with 3 amps NaHCO3 better than NS before cardiac cath3 ml/kg X 1 hr pre-procedure, 6 hrs postOral hydration works, but IV probably betterMerten, JAMA. 2004;291:2328Mueller, Arch Int Med. 2002;162:329Unfortunately no large trials, and one comparing hydration to not, but we assume it’s goodHCO3:Single center RCT in North CarolinaCreatinine >= 1.1Urine pH measured 1st void after infusion of bolus. No diuretics allowed. 13% vs. 2%
37 Preventing Contrast Nephropathy: What is the Evidence? N-acetylcysteineAntioxidantDose: 600 mg BID X 2 daysEarly evidence of dramatic benefit:90% risk reduction vs. placebo(NEJM. 2000;343:180)Subsequent studies mostly favorable but less soSummaryWell-toleratedMay helpAntioxidant: scavenges 02 free radicals, or enhances vasodilatory effects of nitric oxide22 trials compared N-acetyl to placebo; 12 meta-analysesStart 1 day prior if possible
38 Preventing Contrast Nephropathy: Hemofiltration Marenzi. NEJM 2003;349:1333%Hemodialysis - no benefit (Am J Med 2001) and a second study 114 patients - Coronary interventionsHemofiltration: in ICU, 4-6 hr pre and hr postProblems:Criteria for hemodialysisLogistics of hemofiltration
39 Preventing Contrast Nephropathy: Summary of the Evidence YesIdentify high-risk patientsAvoid unnecessary contrastHydrationNoHemodialysisFenoldopamDopamineDiureticsMaybeHemofiltrationAcetylcysteineTheophyllineSevere nephropathy - rare w/ < 100 ml contrastTheophylline - studies conflicting, design heterogeneous
40 Summary Recommendations >= 2 risk factors for contrast nephropathyIV hydration before procedureConsider N-acetylcysteineIso or low-osmolar contrast, minimize amountIV hydration after procedureOf course, monitor for fluid overloadNacetyl: or one study says vit C may work
41 Case: Question #4What is the best strategy to prevent contrast nephropathy?Risk factors for contrast nephropathy? yesC. IV hydration
42 Topics Acute coronary syndromes Insulin in the ICU Clostridium difficileContrast nephropathyPulmonary embolismDiagnosing catheter-related infectionMedication discrepancies
43 Case: Question #4In 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-dimerB. LE doppler ultrasoundC. Pulmonary angiographyD. Conclude that PE is ruled out
44 Diagnostic tests for PE in the hospital D-dimer: unhelpfullow specificity in hospitalized or post-op patients, or with cancerUltrasound: specificity > sensitivity40% with DVT may have asymptomatic PEAngiography: gold standard, invasiveCT: sensitivity for central PE highWhat about subsegmental PE’s?Sensitivity may be as low as 29% - significance?Angio: also low interobserver agreement for subsegmenal PE (45-66%)
45 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 PE3500 patients, 7 nationsPatient follow up 3-12 monthsAfter negative CT:Negative likelihood ratio of clot = 0.07Negative predictive value: 99.1%No benefit to additional studies prior to CT3 different CT techniques15 deaths in follow up due to PE
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: %Visualization of peripheral pulmonary arteriesimproving with better CT techniquesA negative chest CT rules out PENo further testing needed
47 Case: Question #4In 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 difficileContrast nephropathyPulmonary embolismDiagnosing catheter-related infectionMedication discrepancies
49 CaseYour 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 catheterDraw 2 peripheral blood culturesAny diagnostic approach is fine as long as I don’t need to replace the central line
51 Catheter-related bloodstream infection High morbidity and mortality12-27% mortalityProlong hospital stay by 1 weekClinical presentation - nonspecificFever, +/- hypotensionNo other sourceLine site usually cleanIncreased risk with catheter > 7 days
52 Diagnosing intravascular device-related bloodstream infection Remove the catheterQualitative or quantitative tip cultureor Keep the catheterBlood cultures through the catheterCatheter and peripheral blood culturesDifferential time to positivity > 2 hoursPaired quantitative cultures: 3-5 X higher concentration of organisms from catheter
53 Meta-analysis: Methods of diagnosing intravascular device-related bloodstream infection Safdar. Ann Intern Med. 2005;142;451.Highest sensitivityQualitative cultures: catheter tip (90%) or through catheter (87%)Paired quantitative blood cultures (87%)Differential time to positivity (85%)Highest specificityPaired quantitative blood cultures (98%)Quantitative blood culture through catheter (90%)51 studies
54 Summary: diagnostic tests for catheter-related bloodstream infection Best test: Paired quantitative blood culturesDifferential time to positivity also accurate and more widely availableOnly test when catheter infection suspectedPositive predictive value of tests much higher with high clinical suspicionAvoids overuse of antibiotics51 studies
55 Question #5B. Draw blood cultures peripheral and through the catheter
56 Topics Acute coronary syndromes Insulin in the ICU Clostridium difficileContrast nephropathyPulmonary embolismDiagnosing catheter-related infectionMedication discrepancies
57 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?
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 appointmentYou are fine because of your system to meet the JHACO Patient Safety Goal to obtain and document the patient’s medications on admission, and dischargeThe risk is real and a medication discrepancy would increase his risk of readmission
59 JHACO National Patient Safety Goal #8: medication reconciliation process during a transition in carecomparing what medications the patient has been taking previously with the medications about to be providedHospital admission and discharge: important transitions in careDischarge medication list must be communicated to the next provider of care (not just the patient)
60 Post Hospital Medication Discrepancies Coleman. Arch Intern Med What are the prevalence and contributing factors associated with medication discrepancies -prehospital -> discharge -> meds actually taken after dischargeWhat are risk factors for medication discrepancies?Are medication discrepancies associated with readmission?
61 Post Hospital Medication Discrepancies: study population 375 Adults >= 65 years oldAdmitted with common conditions likely to require discharge to skilled nursing facilityCHF, COPD, CAD, DM, stroke, PVD, arrhythmiaBack conditions, hip fractureDiscrepancies = what was patient told vs. what was plannedAll community living adults
62 Categorizing Medication Discrepancies Medication Discrepancy Tool (MDT)Meds assessed by NP hours after discharge to homeDiscrepanciesSystems-based: doctor or systemPatient-based: intentional or non-intentionalDid they try to take it correctly?All community living adults
63 Medication Discrepancies 14% of patients38% of those had > 1 discrepancyAverage # meds: 9 with discrepancy vs. 7 without (p < .001)Common offenders (50% of discrepancies)AnticoagulantsDiuretics, ACE inhibitorsLipid-lowering agentsPPIsAll community living adults
64 Causes of Medication Discrepancies System (49%)Bad instructionsConflicting instructionsDuplicationPatient (51%)Nonintentional nonadherence (34%)$$Intentional nonadherenceBad instructions - illegible, incomplete
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 timeMedication reconciliation in the hospital won’t solve the problemMultiple interventions neededPost discharge follow up reconciliationSystems improvementsPatient education
66 Question #6D. The risk is real and a medication discrepancy would increase his risk of readmission
67 Take Home PointsAcute coronary syndromes: clopidogrel plus ASA before PCI improves outcomesInsulin in the medical ICU: tight glucose control improves survival with ICU stay > 3 daysClostridium difficile: increasingly virulent, increasingly common in the hospital and communityAll community living adults
68 Take Home PointsContrast nephropathy: IV hydration for high risk patientsPE: negative spiral CT rules out clinically important PEDiagnosing catheter-related infection: diagnose with paired catheter and peripheral quantitative cultures, or differential time to positivityMedication discrepancies: common after hospital discharge due to nonintentional non-adherence or systems problemsAll community living adults