Morbidity and Mortality Conference

1. Morbidity and Mortality Conference Gil G. Fareau May 29, 2002 A# 50084135-8

2. 57 year old woman presented to another ER with nausea, vomiting, and headache • Nausea, vomiting, and diarrhea for 6 days. • New headache associated with feeling “off balance” for 2 days. • No fevers, chills, SOB, chest/abdominal pain, or urinary symptoms. No other neurological symptoms

3. Past History Cirrhosis Hepatitis C Hepatic Encephalopathy Type II Diabetes Peripheral Neuropathy GERD, PUD Arthritis +ANA Fibromyalgia Bell’s Palsy Chronic right facial palsy Restless Leg Syndrome Anemia of Chronic Disease Medications Glipizide 20mg qd Carbi/Levodopa 25/100mg qd Lansoprazole 30 mg qd Furosemide 40mg bid Neomycin 500mg bid Potassium Chloride 40meq bid Spironolactone 50mg bid Lactulose 20g bid Insulin 70/30 25 units bid Multivitamin qd

4. History (continued) • Allergies/ADR: penicillin • Social History • Unemployed and on disability • Lived with her daughter • Heavy smoking history • No alcohol use • Family History • Noncontributory

5. Physical Exam • gen: uncomfortable, pale • vitals: T: 37.7, BP: 140/57, P: 98, RR: 18 • heent: + right facial droop, + dry mucus membranes • neck: + tender right strap muscles, supple, no LAD • cvs: rrr, + II/VI systolic murmur • resp: clear to auscultation bilaterally • abd: soft, +diffuse mild tenderness, no masses • ext: no cyanosis, edema • cns: A&Ox3, PERRLA, non-focal

6. Labs: 10.8 130 93 24 LFT’s: normal 7.6 103 5.0 17.8 1.0 31.5 Assessment: Viral gastroenteritis, musculoskeletal headache Plan: - Admit to hospital - IV fluids to rehydrate - Meperidine for headache pain, diazepam for muscle relaxation

7. Outside Hospital Day 2: • Felt improved with no nausea or vomiting and less headache. • Outside Hospital Day 3: • - Minimal headache and deemed fit for discharge. • Two days after discharge: • - Worsening headache, confusion, blurred vision, and recurrent problems with balance. • Exam notable for asterixis, reduced coordination, and poor balance. • Ammonia level of 37, other labs unchanged.

8. Assessment/Plan: • Hepatic encephalopathy secondary to hyponatremia and recent narcotic use. Persistent musculoskeletal headache. • Meperidine and diazepam for headache, IV normal saline to correct her hyponatremia, and ophthamology consult. Head CT: C/W old infarction, no masses or hematomas. Outside Hospital Day 2: -Fever of 38.9 -Decreased visual acuity (right>left), reviewed by ophthamology

9. Lumbar Puncture: WBC: 297 (54% N, 36% L, 10% M) RBC: 7 Protein: 204 Glucose: 3 -Blood cultures taken -Cefotaxime 2g IV q4h -Acyclovir 500mg IV q8h -Vancomycin 500mg IV q6h

10. Outside Hospital Day 3 • Progressively worsening vision • Persistent Confusion • Cryptococcal antigen sent, returns positive with titre of 1:1000 Arrangements made for transfer to Dartmouth-Hitchcock Medical Center

11. Physical Exam at DHMC gen: lethargic, conversant on waking, difficulty with word finding vitals: temp: 38.2, BP: 120/57, P: 90, RR:20, 97%RA heent: oropharynx clear, fundi normal neck: +neck stiffness with pain on flexion ext: + asterixis, no clubbing/cyanosis/edema cns: alert and oriented x 2; vision limited to movement; right VII nerve palsy; tone, power, reflexes and sensation intact; downgoing plantars, finger to nose testing limited by vision.

12. Labs: 10.7 133 99 12 Ca++: 8.8 PT: 15.3 9.0 128 4.5 23 1.0 Mg++: 0.59 INR: 1.3 30.1 Phos: 33 PTT: 30 Ammonia level: 21 Urinalysis: normal Lumbar Puncture: Opening pressure=250 WBC:293 (11% N, 85% L), RBC: 3 Total Protein: 236, Glucose: 5

13. Summary • 57 year old woman • Known diabetes, cirrhosis, anemia • N/V, Headache, Visual loss, Confusion • LP: High WBC, Low Glucose, • Positive Cryptococcal Antigen • Admit to Infectious Disease Service

14. Problem List • Cryptococcal Meningitis • Amphotericin 60mg IV qd • Flucytosine 2grams PO q6h • MRI Brain • HIV test • Neurology Consult • Hepatic Cirrhosis • Follow LFT’s • Continue Lactulose

15. Problem List • Diabetes Mellitus • Diabetic diet • Insulin sliding scale • Anemia • Follow CBC’s • Erythropoietin 40,000 u SQ qweek • Disposition • Poor prognosis given comorbid illnesses, low CSF glucose, and poor mental status prior to treatment. • Living will

16. Hospital Course: Days 2-3 • Resolution of her headache • Improvement in vision (could discern motionless hand) • Mild abdominal discomfort and axterixis • HIV test negative. Cryptococcal Ag in CSF (1:128) * Neurology consult: advised stopping sinemet, minimizing narcotics, consider vasculitic process if no improvement with tx.

17. MRI Flare Images

18. Diffusion Images

19. Enhanced Images

20. Hospital Course: Days 4-6 • Confusion and speech subjectively improved • Vision improving otherwise exam unchanged • Labs: • Creatinine: 1.9 -> 2.2 -> 2.3 • Plan: • Cautious optimism with clinical improvement • Change to liposomal amphotericin • Reduce flucytosine dose to 2grams po q12h

21. Hospital Course: Days 7-10 • Not taking lactulose (causes gagging, vomiting) • Reduced bowel movements • PE: • Vital Signs stable • Somnolent, confused • Distended, tender, tympanitic abdomen with reduced bowel sounds. • + Asterixis

22. Hospital Course: Days 7-10 Labs: Hgb: 10.3  9.6  8.5 Plts: 150  145  136 PT: 18.2, INR: 1.8, PTT: 30 Haptoglobin: 115 TT: 19, Fibr: 275, Dimer: 8330 RTC: 0.8, RTA: 21, RTI: 0.4 Ammonia: 74  76  102 Imaging: abdominal plain film

23. Abdominal Series

24. Hospital Course: Days 7-10 • GI • Ileus • Hepatic Encephalopathy • Dobhoff tube +/- enemas for lactulose delivery • Neomycin 500mg BID • Abdominal US • Heme • Anemia, thrombocytopenia • Check flucytosine level • Transfuse 2 units RBC

25. Hospital Course: Days 11-12 • Agitated overnight, received risperidone • PE: • Increased confusion and drowsiness • Tachycardic, tachypneic, +abdominal distension and tenderness. • Lab: • 140 116 30 145 122 26 ABG: 7.40 19 102 11.4 • 3.7 11 1.6 3.7 9 1.6 • Urine: pH: 5.0, Na: 111, K: 29, Cl: 122, Osm: 375

26. Hospital Course: Days 11-12 Labs (Continued): Flucytosine level: 226 (toxic > 100) Lumbar Puncture: OP: 270 CP: 190 WBC: 387 (98% lymphocytes, 2% neutrophils) RBC: 855, Tot. Prot: 140, Glucose: 79 Cryptococcal Ag. positive (1:2), India Ink Stain negative

27. Meningitis CSF inflammation Toxic flucytosine level D/C flucytosine Continue amphotericin Metabolic Acidosis Type I RTA Due to Amphotericin Replete HCO3 R/O other infections Encephalopathy Hepatic v. meningits v. risperidone Increase lactulose Disposition Patient made DNR per family wishes. Hospital Course: Days 11-12

28. Hospital Course: Days 13-14 PE: Worsening somnolence Tachycardic Tender abdomen Labs: 8.8 150 118 35 13.0 81 3.1 18 2.6 25.8

29. Hospital Course: Days 13-14 Imaging: Repeat abdominal ultrasound

31. Abdominal Ultrasound

32. Hospital Course: Days 13-14 Imaging: Repeat abdominal ultrasound A/P: Meningitis: d/c amphotericin, start fluconazole Hepatic Encephalopathy: increase lactulose, lactulose enemas Abdominal Pain: ? Flucytosine toxicity FEK: worsening renal function

33. Hospital Course: Days 15-16 • Low urine output with intermittent hypotensive episodes • Deeply somnolent and unresponsive • Abdomen distended, with hypoactive bowel sounds • Labs: • WBC:12.4, Hgb:8.9, Plt:86 • BUN:61, Cr:5.3 Family Meeting: Patient made CMO as per her living will Continuous hydromorphone infusion started

34. Hospital Day 17 • The patient was found unresponsive • She was pronounced dead at 10:00am • An autopsy was granted by the family

35. Cirrhosis Trichrome stain H&E stain

36. Portal vein thrombus

37. Cryptococcal meningitis H&E stain GMS stain

38. Cryptococcal encephalitis H&E stain GMS stain

39. Final Pathologic Diagnosis • I. Cryptococcal meningitis • A. Cryptococcal encephalitis • II. Hepatitis C • A.Cirrhosis • 1.Ascites • 2.Ileus • 3.Portal vein thrombosis • 4.Esophageal varices • 5.Hepatic encephlopathy • 6.Spenomegaly • 7.Clinical history of thrombocytopenia • III. Diffuse alveolar damage • IV. Incidental findings • A.Gastric ulcer • B.Chronic cholecystitis and cholelithiasis • C.Right ovarian cystic corpus albicans