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AIDS CLINICAL ROUNDS

Hypothermia in a HIV-infected patient

J. Tyler Lonergan, M.D.

February 8, 2013

Presentation

55 yo HIV+ M BIB family members to ED for worsening generalized weakness x 1 month

Last seen in Owen Clinic several months PTA. At that time off meds for 2 years. CD4 was 205/9% and VL 800,268 c/mL

Poor historian, vague responses

ROS

+ chills and sweats, nausea, anorexia, weight loss, dizziness, and abdominal pain

- confusion, headaches, neck pain, cough, sob, chest pain, diarrhea, dysuria, diarrhea or myalgias

Past Medical History

HIV ‘01 Pulmonary TB ‘01 (treated x 9 months) Cryptococcal Meningitis ‘07 Neurosyphilis ‘08 T2DM ’08: mild, diet controlled CAP ‘09 Hypogonadism GERD

More History

Meds (prescribed but not taking): Kaletra, truvada, mepron, androgel, zantac, gabapentin, vicodin

Allergies: bactrim -> rash ScHx: dentist, lives mostly in

Mexico, bisexual, divorced from wife, no children, + 35 pack year tobacco history, history of etoh and meth abuse

Physical Exam (ED): Gen: wd/wn Hispanic M, lying in bed, lethargic and

slow to respond, slightly confused, shivering VS: T 91.5 F, BP 93/63, HR 70, R 18, O2Sat: 99%

RA H: NCAT, PERRL, O/P clear, MMM N: supple, no lad CV: RRR, nl s1,2, no m,r,g L: CTAB A: nabs, soft, nontender, no masses E: no edema N: A&O X3, CNs intact, nl motor and sensory

exams, brisk DTRs S: intact

Test Results

Chem: Na 130, K 3.5, Cl 98, HCO3 23, BUN 26, Cr 1.91, G 152, Ca 8.5, A 3.6, LFTs: NL, CPK 115, TSH 5.53, Cortisol 29.6, lactate 5, CBC: WBC 5.0 (82%N), H 12.0, Plt 167K

INR 1.2, PTT 37.7 UA: 1+ PRT, WBC 0-2, RBC none Tox: BAL<10, + amphetamines CSF: nl OP, WBC 1, RBC 131, TP

33, G 55, II neg, GS neg

Other study results

ECG: NSR, prolonged QT interval (487ms)

CXR: moderate interstitial pulmonary edema pattern

KUB: nonspecific bowel gas pattern, no evidence of obstruction

CT H (noncontrast): cerebellar and cerebral volume loss greater than expected for age but no acute fracture or evidence of acute hemorrhage, midline shift, or mass effect; no interval change from April ’08 CT

CT A/P (IV contrast): unremarkable

ED course

Management: bair hugger, warmed IVF, stress dose steroids, IV Abx and admit to medicine

Initially worsened; T 90.0oF and BP 81/57. ICU team called but a few hours later T 93.3oF and BP 100/76

Housestaff added clindamycin and primaquine for PJP coverage and tamiflu for influenza coverage. Isolated and active rewarming continued

Hospital Day #2

Tmax 103.3, 4 cm x 4 cm R supraclavicular indurated and nontender mass first noted

HNS consulted Recommended CT neck and chest

and FNA of LN

Hospital Days #3 and 4

Daily fevers CT N (w/ contrast): necrotic and enlarged

lymph nodes in R SC area and R upper mediastinum

CT C (w/ contrast): miliary pattern of lung nodules

Labs: Cr 0.86, Influenza A, B negative, Blood cultures x 4 NG (x one + CNS), CRAG neg, Cocci CF/ID neg, U histo Ag neg, Aspergillus Galactomannan neg, U Legionella neg, CMV DNA PCR neg, RPR 1:8 (down from 1:16), QFT negative, CD4 = 25/10%, VL 195,976, CSF: HSV PCR, VDRL negative

Hospital Day #5

T max 104.3oF HNS: flexible nasopharyngo-

laryngocscopy negative for lesions and FNA of R SC LNs done

FNA path: suggestive of granulomas RIPE + A started for TB and MAI

LN FNA – 20x

Hospital Day # 6

Feeling better FNA studies including flow

cytometry and AFB smear negative ENT reconsulted for more LN tissue Sputum AFB smears x 3 negative

LN Core Bx: H&E 10X

LN Core Bx- H&E 20X

LN Core Bx - AFB 60X

Hospital Day #7

Afebrile x 48 hours, discharged (after consultation with DPH) on RIPE + A (DOT), dapsone and outpatient f/up

One month later AFB cultures from sputum, FNA and blood grew M. Tuberculosis

Conclusion: hypothermia was due to M. TB sepsis (Landouzy sepsis)

Temperature Curve

TB therapy started

Hypothermia

Definition Pathophysiology Causes Clinical Manifestations Laboratory Evaluation Management

Definition and Classification Core Temperature <35oC (<95oF) Mild: 32-25oC (90-95oF) Moderate: 28-32oC (82-90oF) Severe: <28oC (<82oF)

Pathophysiology

Body temperature balance between heat production and loss Heat generated by cellular metabolism

(mostly in heart and liver) Heat lost by skin and lungs via:

Evaporation Radiation Conduction Convection

Pathophysiology - 2

Body’s response:

Hypothalamus (increase heat production)

Shivering

Stimulation of thyroid, catecholamine and adrenal activity

Sympathetic nervous system (decrease heat loss)

Vasoconstriction; reduces blood flow to peripheral tissues

Causes

Increased heat loss: Environmental exposure Induced vasodilation (eg, medications,

etoh, toxins) Skin Disorders (eg, burns, psoriasis,

exfoliative dermatitis) Iatrogenic (eg, cold infusion,

emergency deliveries, cardiopulmonary bypass, CRRT)

Causes

Decreased Heat Production Endocrinologic Failure (eg,

hypopituitarism, hypoadrenalism, hypothyroidism)

Insufficient Fuel (eg, hypoglycemia, malnutrition)

Neuromuscular inefficiency (eg, extremes of age, impaired shivering, inactivity)

Causes

Impaired Thermoregulation Peripheral (eg, spinal cord transection,

neuropathies, diabetes mellitus) Central (eg, CVA, SAH, Parkinsonism,

hypothalamic dysfunction, MS, anorexia, drugs including anxiolytics, antidepressants, antimanic agents, antipsychotics, opioids, antihyperglycemics, beta blockers)

Other Causes

Sepsis Pancreatitis Carcinomatosis Uremia Vascular Insufficiency Trauma

Hypothermia and Tuberculosis

4 cases reported in the literature All associated with meningitis 3 also associated with hydrocephalus 2 reversed after placement of ventricular

shunt 2 cases thought related to pressure on

hypothalamus and one due to vascular lesion in hypothalamus

No case like this one (hypothermia in TB without meningeal involvement) found in literature

Clinical Presentation

Mild: tachypnea, tachycardia, ataxia, dysarthria, confusion, shivering

Moderate: hypoventilation, progressive bradycardia, hypotension, atrial and ventricular arrhythmias, CNS depression, loss of shivering,

Clinical Presentation

Severe: pulmonary edema, apnea, worsening bradycardia and hypotension, ventricular fibrillation (<28 C) and asytole (<20 C), coma, muscle rigidity

Laboratory Findings

ABG: metabolic acidosis, respiratory alkalosis, or both

Lytes: no consistent abnormalities Glucose: increased, decreased or normal WBC and Platelets: decreased due to

splenic sequestration Hemoglobin: increased due to

hemoconcentration

Other Studies Lipase: may be increased due to

hypothermia induced pancreatitis PT/PTT: increased in vivo due to inhibition of

coagulation cascade, despite normal reported values

ECG: prolongation of PR, QRS, QT intervals, ST segment elevation, T wave inversions, Osborn J waves, atrial fibrillation or sinus bradycardia

CXR: aspiration pna, vascular congestion, pulmonary edema

J (Osborn) Wave

Management

Management

Intubate obtunded patients and those with bronchorrhea

Treat hypotension with warmed (42oC) NS, dopamine if necessary

Avoid rough movements and activity which may induce ventricular fibrillation

Rewarming Strategies

Mild Passive external rewarming (blankets)

Moderate Above + active external rewarming (forced

warm air applied to skin via Bair Hugger blankets)

Severe Above + active internal (core) rewarming

warm IVF (40-42oC) warmed humidified O2

irrigation of body cavities with warmed crystalloid extracorporeal blood rewarming (eg hemodialysis)