Emergency Medicine Rounds

1. Emergency Medicine Rounds Dr. Edward Les September 26, 2002

2. Case 16 year old girl c/o intermittent fever and bilateral leg pain x 5 days • unable to walk since yesterday • feet,calves painful • nauseated; emesis x1 • L arm, R abdo pain as well • decreased energy/appetite • dry cough

3. w/i clinic x 2 in past 5 days • Rx’d tylenol and ibuprofen – relief of symptoms with same • CBC done @ 2nd w/i visit (3 days prior to ER): • WBC 9.9, no shift • Hb 142 • Platelets 121 • U/A: • 10-20 WBC, 5-10 RBC, many epith

4. PMH – noted at triage: VSD • scheduled for f/u echo following week

5. Course in ER *Had taken Tylenol and ibuprofen 1 hour prior to presentation • Initial VS: • T 37.6, P 108, BP 97/47 • Noted to be somewhat lethargic and unable to bear weight with some L leg swelling by triage nurse; tender RUQ

6. Course in ER • Seen by ER doc 1 hour after triage: • Continued afebrile • Symptoms abated since arrival • Documented exam - generally normal apart from cardiac murmur • Note made of low platelet count and abnormal U/A • Discharged – dx: viral syndrome with myalgia

7. 2 days later…… Presented to FHH with ongoing intermittent fever, migratory arthritis, abdo pain, N/V, sore throat Subsequently found to have endocarditis as demonstrated by transesophageal echo and Group C Strep bacteremia

8. Complicated course in hospital • Abdominal wall abscess – sx drained • Pleural effusions – chest tube • Coagulopathy • Pericardial effusion/tamponade – drained 300 mL Rx with IV Pen V and gent, then Pen V alone x 4 weeks *Noted to have very poor dental hygiene

9. Her cardiac anatomy Based on echo 1 year prior to presentation • restrictive perimembranous VSD • ~ 4 mm • L R flow gradient 78 mm Hg • LV size - upper limit of normal

10. Infective Endocarditisin childhood • Background • Etiology • Epidemiology • Pathogenesis • Clinical manifestations • Diagnosis • Prognosis/complications • Treatment • Prevention

11. Pediatric infective endocarditis • Acute vs subacute • Bacterial, fungal, viral • Acute: usually S. aureus, S. pyogenes, S pneumoniae etc • Subacute: usually S. viridans or enterococcus • Lots of overlap better to classify simply by etiologic agent • Remains significant cause of M&M despite advances in management and prophylaxis

12. Why? • Diagnosis can be difficult when delayed • Physicians/dentists/public not sufficiently aware of threat of IE and preventative measures available • Special risk groups have emerged • Survivors of cardiac surgery • Patients taking immunosuppressants • Patients with chronic IV catheters/ increased PICU complexity • IV narcotics users

13. Epidemiology • 1 in 1280 pediatric admissions per year? Am Heart J. 1984:107:1235-1240 • Probably higher now • Most often a complication of congenital or rheumatic heart disease • Can also occur in children without a cardiac malformation • 8-10% of cases: usually S. aureus • Rare in infancy • following open heart sx • NICU kiddies with central lines

14. Etiology

15. Culture negative • 5-10% of cases • Fastidious organisms or anaerobes • Prior antibiotic treatment • Non-bacterial • R-sided endocarditis

16. pathogenesis Intact cardiac endothelium: poor stimulation of coagulation weakly receptive to bacterial attachment • Valve surface altered to produce suitable site for bacterial attachment and colonization • Platelets and fibrin deposition in the formation of sterile vegetation – Nonbacterial Thrombotic Endocarditis (NBTE) • Bacteria reach this site and produce colonization • The surface is covered with platelets and fibrin  clot propogates over deposited bacteria • Further bacterial multiplication and vegetation growth - 107-1010 cfu/g of tissue

17. Localization of IE • high pressure areas: down stream from sites where blood flows at high velocity through a narrow orifice Venturi effect: maximal deposition of bacteria in low-pressure sink e.g.: atrial surface of mitral valve (MR) ventricular aspect of aortic valve (AR) RV wall (restrictive VSD)

18. Transient bacteremia Occurs whenever a mucosal surface heavily colonized with bacteria is traumatized If preexistent NBTE, it may result in colonization and IE • Surgical or dental procedures can be implicated in approximately 65% of cases • Poor dental hygiene particular risk factor in kids with cyanotic CHD

19. Generally… • Patients with IE and no underlying heart disease: Staph aureus more common • S. viridans more common after dental procedures • Group D enterococci more often after lower bowel or genitourinary manipulation • Pseudomonas or Serratia – IV drug use • Fungal organisms after open heart surgery

20. Sticky bugs • Organisms more frequently associated with IE adhere more readily to normal leaflets in vitro e.g. 1. FimA is a surface adhesin of S.viridans that serves as an important colonization factor. Homologues of fimA genes were found in many S. viridans strains and enterococci. 2. Fibronectin is implicated as the host receptor within NBTE. Low-fibronectin-binding mutants of S. aureus have decreased ability to produce IE. 3. Gm + coccus resistant to phagocytosis, platelet microbicidal proteins (PMP), and complement-mediated killing

21. Who to worry about? • High risk: • Children with VSD’s, L-sided valvular disease, and systemic-pulmonary arterial communications  Most frequent structural lesions associated with IE: • Tetralogy of Fallot • VSD (esp restrictive) • Aortic stenosis/coarctation • PDA • TGV • B-T shunts • Valve replacements/valved conduits • Low risk: • pulmonic stenosis, ASD

22. Others at risk… • Congenital bicuspid aortic valve • Mitral valve prolapse with regurg • Hypertrophic cardiomyopathy • Ventriculo-atrial shunts

23. Immunopathologic factors IE cause both humoral and cellular responses • Rheumatoid factor: • titers correlate with the level of hypergammaglobulinemia and decrease with therapy) • Antinuclear antibodies: • may contribute to the musculoskeletal manifestations, low-grade fever, or pleuritic pain • Circulating immune complexes: • Connected with long duration of illness, extravascular manifestations, hypocomplementemia • May cause diffuse glomerulonephritis, and some of the peripheral manifestations such as Osler nodes

24. Clinical manifestations • Relate to 4 underlying phenomena: • Bacteremia (or fungemia) • Valvulitis • Immunologic response • Emboli

25. Fever Absent in 5-10% of cases Staph: hi spiking Strep: low grade Chills Chest and abdominal pain Arthralgia, myalgia Dyspnea Malaise Night sweats Weight loss CNS manifestations Stroke, seizures, headache Symptoms • Presentation is a • continuum

26. Fever Tachycardia Embolic phenomena Roth spots Petechiae Splinter hemorrhages Osler’s nodes CNS lesions Janeway lesions Splenomegaly Arthritis New or ’ing murmur CHF Arrythmias Metastatic infection Arthritis Meningitis Mycotic arterial aneurysm Pericarditis Abscesses Septic pulmonary emboli Clubbing Long-term signs

27. Famous but rare janeway Splinter hemorrhage

28. Lab • Hematology • Anemia: normochromic, normocytic, • Thrombocytopenia (5-15%) • Leukocytosis (20-30%) • Elevated ESR, with mean value of 57mm/hr (90-100%) • Hypergammaglobulinemia (20-30%) • Urinalysis • Proteinuria (50-65%) • Microscopic hematuria (30-60%) • Red cell casts (12%)

29. Lab • Serology • Rheumatoid factor (40-50%) • Circulating immune complexes • ANA • hypocomplementemia • Blood culture • Most important lab test • Positive cultures in 90-95% of cases

30. Sign/sx/lab Very common Fever Positive BC  ESR or CRP Common HA, myalgia, malaise Anemia Hematuria Leukocytosis RF Infrequent New or ’ing heart murmur CHF Petechiae Peripheral emboli Splenomegaly Neuro ’s Echocardiographic vegetations Rare Osler’s nodes Janeway lesion Roth spots Splinter hemorrhages

31. Diagnosis • Need a HIGH index of suspicion in a child with an underlying contributory factor • Modified Duke’s criteria Li JS et al. Clin Infect Dis 2000: 30:633-8. • Sensitivity >80% • NPV 92% • Uses pathologic criteria and major and minor clinical criteria

32. Typical bug from 2 separate BC’s, or Enterococcus in absence of primary focus, or Persistently + BC with bug consistent with IE drawn >12 h apart, or All 3 or a majority of 4 or more separate BC’s with 1st and last drawn at least 1 h apart, or + Q fever serology + echo for IE: oscillating intracardiac mass, on valve or supporting structures, or in path of regurgitant jets, or on implanted materials, in the absence of alternative anatomic explanation, or Abscess, or New partial dehiscence of prosthetic valve, or New valvular regurgitation Duke’s – major clinical criteria Evidence of endocardial involvement Positive blood culture for IE

33. Predisposing heart condition or IV drug use Fever > 38 C 3.Vascular phenomena Major arterial emboli Septic pulmonary infarcts Mycotic aneurysm Intracranial hemorrhage Conjunctival hemorrhages Janeway lesions 4.Immunologic phenomena Osler’s nodes Roth spots Glomerulonephritis Rheumatoid factor 5.Microbiologic evidence + BC but not meeting major criterion, or Serologic evidence of active infection with organism consistent with IE Duke’s – minor clinical criteria

34. Possible IE Rejected Definite IE • Pathologic criteria • Microorganisms • by culture or histology • in a lesion/vegetation/ • intracardiac abscess • or • Lesions • vegetation or intracardiac • abscess present, • Clinical criteria • 2 major criteria, or • 1 major and 3 minor, or • 5 minor At least 1 major and 1 minor, or 3 minor Alternative diagnosis for manifestations of IE or Resolution of manifestations with abx <4 days or No path evidence of IE at surgery or autopsy after abx for < 4 days

35. Blood cultures • Prior to antibiotics • Prep the skin • 70% isopropyl alcohol, then iodine – let dry • Peripheral blood • Timing doesn’t matter • Need lots of blood!! • 20 ml/draw in adults; 1-2 mL/draw in neonates, 2-3 infants, 3-5 older kids, 10-20 adolescents • Low-grade bacteremia (1-10 cfu/mL venous blood • Most of the bugs are buried - most of the damage is occuring away from the surface (valve-ring abscesses and ruptured chordae)

36. Blood cultures in IE Towns, ML and LB Reller. ID Clinics NA 2002; 16(2) • Acute IE: 2-3 cultures from several venipuncture sites w/i 5 minutes of each other – then treat • Subacute IE: several BC’s spaced 30 minutes to an hour apart prior to instituting empiric abx therapy • Multiple cultures: • More blood = single most important factor for successful recovery of bug • Rate of positivity increases as more cultures are obtained (up to a point) • Need multiple BC’s to meet Duke criteria for diagnosis • ONE BC is inadequate!!! • Doesn’t maximize chance of isolating etiologic agent • Cannot demonstrate presence of continuous bacteremia • Cannot distinguish true bacteremia from contamination

37. Blood volume related to culture positivity Towns, ML and LB Reller. ID Clinics NA 2002; 16(2)

38. Notify the lab of suspected IE • May need prolonged culture (> 7 days) on enriched media to detect nutritionally variant and fastidious bacteria or fungi • Indicate if received abx prior to collection

39. Dx: procedures • Echo • TTE • rapid, noninvasive • specificity: 98% • sensitivity: <60% • TEE • improved spatial resolution • specificity: 94% (prosthetic valve: 88-100%) • sensitivity: 76-100% (prosthetic valve: 86-94%) Helps predict risk of embolism • > 1 cm or fungating • Location on AV or anterior MV

40. Remember ….. Absence of vegetations does not exclude IE Vegetations are often not visualized in the early phases or in patients with complex CHD

41. Dx: procedures • EKG • May show arrhythmias or conduction disturbances

42. Prognosis • Pre-antibiotic era – fatal • With abx – mortality still 25-50% • Serious morbidity in 50-60% • CHF in 30%: valvular veggies, myocardial abscesses, pericardial effusions, ruptured sinus of Valsalva, acquired VSD, heart block • Systemic emboli: stroke, abscesses, osteomyelitis, arthritis, renal impairment, meningitis • Pulmonary emboli • Mycotic aneurysms

43. Veggies eat your heart out

44. Mycotic aneurysms • Develop during active IE • More common with S.viridans • May arise by the following mechanisms: • direct bacterial invasion of the arterial wall with subsequent abscess formation or rupture • septic or bland embolic occlusion of the vasa vasorum • immune complex deposition with resultant injury to arterial wall • Tend to occur at bifurcation areas; middle cerebral artery is most common • Clinically silent until rupture

45. Empiric abx: Vanco + gent or Pen + gent (?talk to ID) Treat CHF if present Admit I.E. in the E.D.Treatment

46. Treatment • Prolonged ; usually at least 4-6 weeks abx • hi #’s or bugs • relatively protected locale; bacteria relatively metabolically quiescent within the veggies • need b/w 5 and 20 times MIC

47. refractory CHF physiologically significant valve dysfunction as demonstrated by echo >2 serious systemic embolic episode uncontrolled infection/ineffective antimicrobial therapy resection of mycotic aneurysms most cases of prosthetic valve IE (caused by more antibiotic-resistant pathogens) local suppurative complications including perivalvular or myocardial abscesses Surgical intervention:indications

48. Surgical therapy:echo features • Persistent vegetations after a major systemic embolic episode • Large (>1cm diameter) anterior mitral valve vegetation • Increase in vegetation size 4 weeks after antibiotic therapy • Acute mitral insufficiency • Valve perforation or rupture • Periannular extension of infection

49. Prevention:in at risk groups • Antimicrobrial prophylaxis prior to various procedures • Proper dental care and hygiene • Vigorous treatment of sepsis and local infections • Careful asepsis during heart surgery and catheterization

50. I.E. prophyaxis in the E.D. What’s the evidence? • Nonexistent: no RCT • Uncommon disease even in highest risk kids • Bacteremia from dental procedures accounts for only ~10% of cases • Efficacy of prophylaxis only ~50%