Hepatic Encephalopathy… Maybe?

Case ConferenceFebruary 19th, 2013

Scott Laura

• Confusion and worsening back pain for 2 weeks

Chief Complaint

• 55 y.o. male with hx of HIV (CD4 count 01/10 was 23: Below 200 since 2005), emphysema, Hep B and C, depression, AoCD, GERD, chronic back pain, who presents with confusion and back pain x 2 weeks that has progressively worsened.

• Pt presented to ED under his own volition, with complaint of pain in his “bones and back”

• Also reported minimal weakness.

HPI

• Patient stated he had been confused since a female acquaintance stole his home prescription of morphine. – On chronic pain meds for LBP.

• Unsure of cause• No previous mention in chart review

– He was slow to answer questions and perseverating during exam.

• Patient was noted to be removing IV access and agitated

HPI

• HIV with CD4 of 23 and % of 4.8 (1/10)• Pulmonary MAC

– Diagnosed in 4/2010 treated with Clarithromycin, Ethambutol and Rifampin.

• Smear negative 1/2011 x 1– Followed by NO/AIDS and pulmonary (1 visit in 1/11)

• Hep B and Hep C• Emphysema • Anemia of Chronic Disease • Chronic low back pain• Depression• Poly-substance abuse

Past Medical History

• No Known Surgical Procedures – Per chart review

Past Surgical History

• Morphine of unknown dosage/prescriber• Per Chart review Jan 2011

– Azithromycin 1200mg weekly– Bactrim DS 1 tab daily– Ethambutol 400mg 2.5 tabs daily– Clarithromycin 500mg 2 tabs daily– Rifabutin 150mg 3 tabs daily– Raltegravir 400mg BID– Abacavir/Lamivudine 600/300mg daily– Albuterol HFA 2 puffs q 4-6 hours PRN: SOB/wheezing– Tiatropium 18mcg daily– Fluoxetine 20mg daily– Ibuprofen 200mg 1-2 tabs q 8 hours PRN: pain– Lansoprazole 30mg daily

Medications

• IV Contrast: Anaphylaxis• Penicillins: Throat Swelling

Allergies

• Father passed away from unknown causes at 34 y/o.

• Maternal grandfather died of mesothelioma at unknown age.

• Mother unknown.

Family History

• Per Chart Review– 80 year tobacco history– Denied current alcohol use– History of Heroin Use – unknown

quantity/duration• Heterosexual• Incarcerated 3 years prior• Has lived in homeless shelters in past• Worked as a “boiler-maker” for ~10 yrs.

Social History

• PCP with NO AIDS task force.• Unknown Flu, pneumo, tetanus. • No colonoscopy per records.

Health Maintenance

• Gen: No weight changes, fever or chills• HEENT: No visual changes, sore throat, rhinorrhea but +

conjunctival erythema • CV: No chest pain, palpitations, SOB, DOE, orthopnea or PND• RESP: No cough, SOB• GI: No N/V/Diarrhea/melena/BRBPR,

– + constipation • Skin: No new rashes• GU: Denied Dysuria or change in frequency• Neuro: + for dizziness • Musculoskeletal: Low back pain x 1 year acutely exacerbated 2

weeks prior

ROS Limited

• Vitals– Triage

• T 99.1 BP 134/82 P 105 RR 19 O2 100% on RA• 6’ 68kg BMI 20

– Exam• T 98.3 BP 121/68 P 90 RR 28 O2 100% on RA

Physical Exam

• GENERAL: – Thin, cachectic & dishelved.– Altered with slurred speech and difficult to understand.– Uncooperative with exam

• HEENT: – Normocephalic, atraumatic. – MMM with no dentition. – PERRL, EOMI, unable to assess optic nerve. No scleral icterus – No obviously elevated JVP.

• CARDIOVASCULAR: – Regular rate and rhythm. No murmurs, S3 or S4 noted

• RESPIRATORY: – CTA however patient uncooperative with deep inspiration and palpation

Physical Exam

• ABDOMEN: – Bowel sounds present. – Soft. Nontender. Nondistended. No organomegaly.– No rebound, guarding , shifting dullness, fluid wave, or caput medusa

appreciated.• EXTREMITIES:

– No clubbing, cyanosis, or edema.• Back:

– Uncooperative with straight leg raise or range of motion.– Lumbar paraspinal muscle TTP

• Skin: – Multiple tattoos

• Some professional and multiple homemade. – No signs of telangiectasias

Physical Exam

• NEUROLOGIC: – Mental: Oriented to self and place, not to time (day, month

or year)– Sensation intact to light touch. – Reflexes unable to assess – Strength is 5/5 bilaterally in the upper and lower

extremities. – Cerebellar function: Patient seen standing and ambulating

on exam – CN II-XII: EOMI intact, PERRLA, sensation intact to light

touch, raises eyebrows, closes eyes tight, symmetric faces

Physical Exam

• NEUROLOGIC: – CN II

• Not assessed– CNIII, IV, VI

• EOMI intact and PERRLA B/L– CN V

• Sensation intact to light touch B/L– CN VII

• Raises eyebrows & closes eyes tight symmetrical B/L– CN VIII

• Gross hearing intact – CN IX, X

• Phonation and swallowing intact– CN XI

• Not assessed secondary to being un-cooperative but moving shoulders and neck– CN XII

• Tongue appeared mid-line

Physical Exam

Labs Admit

6.5

10.913.5-17.5

31.7 40-51

121 130-400

95

14

140 102 56(7-25)

4.1 20(24-32)

3.3(0.7-1.4)

92

15(8.4-10.3)

TP ALB AST ALT AP TB11

(6-8)3.2(3.4-5.0)

81(<45)

47(<46)

50 0.8

Ammonia 80 (9-35)

LA 2.1

Aceta <10

Salicylate <4

N 71 L 20 M 9 E 0 B 0

CCa 15.64 Mg 2.4 P 3.7PT 13.0 INR 1.2 PTT 35.3

Baseline labs:Cr 1.0-1.5 from 12/05 – 3/10Ca 8.4-9.1 from 12/05 - 3/10

Labs Admit

UASg 1.020pH 5.0Prot 25Glu NormKet NegBili NegBlood 25Nitrite NegUrobil NormLE Neg

UARBC 0-2WBC 6-10 (0-5)SqEp 20-100Bact NegCasts 0-2

Hyaline & calcium oxalate crystals

Methanol <4

Ethanol <15

Isopropanol <4

Opiate met +

THC +

Cocaine met +

CXRNo acute abnormality identified

• Overnight/Day 1 – Underwent CT head W/O contrast – Patient received Ativan 2 mg for LP around

midnight – Did not receive Lactulose – X ray of lumber spine

• Multilevel degenerative changes in the spine with no significant interval change.

– Urine: No organisms on smear– Upep/Spep Pending

Hospital Coarse

CT BrainAtrophy and chronic microvascular ischemic changes. Left mastoid

disease. No acute intracranial findings.

• LP (Tube 4)– CSF Clear– WBC 4 (differential not performed for <6)– RBC 12 (0-5)– LDH 23– Glucose 55 (40-70)– Total Protein 40.2 (15-45)– Crypto Antigen Negative

• Gram Stain:– No Organisms

Labs

Labs Day 1

141 108 54

3.8 18 3.04 90

13.5

TP ALB AST ALT AP TB

9.4 2.6 65 38 43 0.9

Ammonia 80 -> 118

LA 1.8

TSH 0.31 (0.5-5.0)

FT4 0.8

CCa 15.58 Mg 2.2 P 3.4

Baseline labs:Cr 1.0-1.5 from 12/05 – 3/10Ca 8.4-9.1 from 12/05 - 3/10

PT 13 INR 1.2 PTT 32.8

• CBC Stable but platelets clumped

Blood

Ferritin 454 (20-300)

Iron 109

Transferrin 152 (200-360)

TIBC 198 (250-425)

Iron Sat 55 (15-50)

Folate 6.1

Vit B12 330

Urine Creatinine 229.5Na 36FENA 0.34TP/Cr ratio 298 (<200)

Additional Labs

Hospital Coarse

• Day 2– Transferred to floor overnight – Received 1-2 doses of Lactulose – Began vomiting, no hematemesis noted

Ammonia 80 > 118 > 125 > 95

BUN 56 > 54 > 50

Creatinine 3.3 > 3.04 > 2.97

Calcium 15 > 13.5 > 13.7 > 14.2

• Day 3:– Patient received Ativan 2 mg overnight for “excessive

restlessness”– Mental status waxing and waning, AM of Day 3 he was

able to answer questions but still with slurred speech and confusion

– Outputs unrecorded– Calcium still elevated with only slight improvement in renal

function• Calcitonin 250U Q12 started with considerable increase in

IVFs

Hospital Coarse

Ammonia 80 > 118 > 125 > 95 > 112

BUN 56 > 54 > 50 > 51

Creatinine 3.3 > 3.04 > 2.97 > 2.75

Calcium 15 > 13.5 > 13.7 > 14.2 > 12.9

PTH 9 (12-65)

• Late that afternoon (Day 3)Hospital Coarse

Large Monoclonal Band in Beta Region Adequate amount of normal serum immunoglobulin presentIgM KAPPA specificity

UPEP: Extra Band in the mid Gamma RegionImmunofixation: Free Kappa Light Chains

Heme-Onc consulted

• Day 4:– Mental status still waxing and waning, he was able

to answer questions but still with slurred speech and confusion

– Received Lactulose as scheduled – Net negative 10 Liters from admission

• 4.7 Liters in past 24 hrs

Hospital Coarse

Ammonia 80 > 118 > 125 > 95 > 112 > cancelled

BUN 56 > 54 > 50 > 49 > 60

Creatinine 3.3 > 3.04 > 2.97 > 2.91 > 2.24

Calcium 15 > 13.5 > 13.7 > 14.2 > 12.9 > 12.6

• Day 4:– Heme/Onc:

• Kappa/lamba ratio, IgM, IgG, IgD, and beta-2 microglobulin ordered

• Bone Marrow Biopsy pending• Decadron 40 mg IV Q24• Pamindronate 60 IV

– X-ray Bone survey completed and compared with completed CT of Head (Day1).

– CT chest/abdomen/pelvis

Hospital Coarse

Bone Survey

CT abdomen/pelvis

CT Abd/Pelvis without contrast

CT Abd/Pelvis without contrast

CT of Chest without contrast

• Day 5:– Patient found in afternoon

with feces covering patient and bed

– NG tube placed– Pt transferred to ICU for

worsening mental status and higher level of care

– Added Rifaximin

Hospital Coarse

Kappa/lambda Pending

IgM 5812 (40-168)

IgG 726

IgA 83

Beta-2 Microglobulin 7.5(0.6-2.4)

Ammonia 80 > 118 > 125 > 95 > 112 > 194

BUN 56 > 54 > 50 > 49 > 60 > 70

Creatinine 3.3 > 3.04 > 2.97 > 2.91 > 2.24 > 2.14

Calcium 15 > 13.5 > 13.7 > 14.2 > 12.9 > 12.6 > 11.5

ICU Transfer Labs

7.48.9

25.499

95

13.6

144 114 69

3.9 18 2.16 107

12.3

TP ALB AST ALT AP TB

9.5 2.3 52 34 32 0.7

Ammonia 194

LA 2.3

PT 16.6

INR 1.5

N74 B8 L11 M4 Meta2 Mylo1CCa 13.66 Mg 1.8 P 2.2

ROULEAUX SEEN ON SMEAR

• Day 6:– Dark Brown NG Tube output

sent for occult blood testing returned as positive

– H/H stable– Plasmaphoresis initiated – Albumin Infusion– Bone Marrow Biopsy done

Hospital Coarse

Ammonia 80 > 118 > 125 > 95 > 112 > 194 > 146

BUN 56 > 54 > 50 > 49 > 60 > 70 > 68

Creatinine 3.3 > 3.04 > 2.97 > 2.91 > 2.24 > 2.14 > 2.05

Calcium 15 > 13.5 > 13.7 > 14.2 > 12.9 > 12.6 > 11.5 > 10.9

Serum Viscosity 4.8 RR(1.6-1.9)

Flow Cytometry APPROXIMATELY 22.3% OF TOTAL CELLS ANALYZED IN THIS BONE MARROW ASPIRATE SAMPLE ARE KAPPA LIGHT CHAIN RESTRICTED PLASMA CELLS THAT ARE BRIGHT CD138+, BRIGHT CD38+, AND DIM CD45+. THEY ARE NEGATIVE FOR CD117 AND CD56.

MATURE LYMPHOCYTES COMPRISE APPROXIMATELY 11% OF TOTAL CELLS AND CONSIST OF A MIXTURE OF T AND B CELLS. THE T CELLS SHOW AN INVERTED CD4:CD8 RATIO, CONSISTENT WITH THE PATIENT'S HIV STATUS. THE B CELLS SHOW NO EVIDENCE OF LIGHT CHAIN RESTRICTION.

CONSISTENT WITH PLASMA CELL MYELOMA.

Bone Marrow Biopsy

Aspirate smear, 20xNumerous atypical plasma cells with variable size, prominent nucleoli

Bone Marrow Biopsy

Aspirate 100x, binucleated plasma cell

Bone Marrow BiopsyCore biopsy, 2xHypercellular marrow, bone destruction.

Bone Marrow BiopsyMarrow, 20xSheets of plasma cellBone destruction

Osteoclast

Bone Marrow Biopsy

Marrow, 40xSheets of plasma cellBone destruction

CD138 stainHighlights the numerous plasma cells

Bone Marrow Biopsy

Bone Marrow Biopsy

Ki-67 stainProliferation index marker

• Day 7:– Multiple BMs overnight– Improving Mental Status – Started Feeds Per NGT– Consulted Urology for hyrdonephrosis

• Deferred to IR– IVF and lasix discontinued

• Calcitonin continued

Hospital Coarse

Ammonia 80 > 118 > 125 > 95 > 112 > 194 > 146 > 159

BUN 56 > 54 > 50 > 49 > 60 > 70 > 68 > 54

Creatinine 3.3 > 3.04 > 2.97 > 2.91 > 2.24 > 2.14 > 2.05 > 1.75

Calcium 15 > 13.5 > 13.7 > 14.2 > 12.9 > 12.6 > 11.5 > 10.9 > 8.5

• Day 8:– Continued multiple BMs overnight– Mental Status still improving– Calcitonin discontinued– IR consult for biopsy of

retroperitoneal mass and access for chemo

Hospital Coarse

Ammonia 80 > 118 > 125 > 95 > 112 > 194 > 146 > 159

BUN 56 > 54 > 50 > 49 > 60 > 70 > 68 > 54 > 51

Creatinine 3.3 > 3.04 > 2.97 > 2.91 > 2.24 > 2.14 > 2.05 > 1.75 > 1.71

Calcium 15 > 13.5 > 13.7 > 14.2 > 12.9 > 12.6 > 11.5 > 10.9 > 8.5 > 8

– Day 9: Ativan given for agitation• Worsening mental status

– Day 10: IR placed nephrostomy tube and performed biopsy of retroperitoneal mass.

• Anaplastic appearing cells, many with plasmacytoid features.

• The malignant cells stain with CD138 andare negative for CD3, CD20, and CD56. Ki-67 stains approximately 90% of cells.

• Findings most consistent with diagnosis of a plasma cell neoplasm, most likely plasma cell myeloma

– CT head (no changes)

Hospital Coarse

Hospital Coarse

– Day 11: Corrected Sodium, but physically abusive to staff.

• No family/contacts could be reached.• Patients mental status improved.• Ethics and Palliative care consult placed.• Patient had coherent conversation with Oncology team

– Understood disease process– Wished to not pursue further treatment.

– Day 12: Two of patient’s friends were located, meeting with ethics committee.

• They stated prior to presentation, patient was usual self [walking, riding bikes, buses etc].

– Patient has made comments in recent past of “ready to go.”

– Estranged son in FL [unk name or contact info]. – Patient status changed to DNR/DNI– Transfer to Hospice

Hospital Coarse

Thank You