Signing off...

This is the last blog post of the year for me...


I've enjoyed managing the TWH Tangents and TGH Horses and Zebras Blogs for 2009-2010. I hope you found them helpful


Your CMR 2009-2010

Pancytopenia

Today we discussed an approach to the patient with pancytopenia

This is an indication for a bone marrow aspirate and biopsy, which usually shows increased or decreased marrow cells:

Hypocellular marrow
-Marrow toxins: May be dose-dependent, predictable as with chemotherapeutic agents, immunomodulators (methotrexate, cyclophosphamide, etc) or idiosyncratic (chloramphenicol, sulfa drugs, phenytoin, many others); radiation, EtOH
-Infection: Parvovirus B12, EBV, HIV, HHV-6, viral hepatitis; severe sepsis
-Immune: SLE, RA (rare), graft-versus-host
-PNH
-Idiopathic stem cell failure

Hypercellular marrow
-MDS, leukemias, lymphomas, myeloma
-Nutritional- severe megaloblastic anemia (B12, folate)
-Marrow replacement/infiltration: myelophthisic anemia , myelofibrosis, granulomatous disease (TB, sarcoid, fungal), solid tumor metastases (prostate and breast are most common)

The topic of the MGUS and multiple myeloma 'spectrum' came up. Here are some helpful criteria based on the NEJM review paper cited below:

MGUS
Marrow plasma cells less than 10% and M-protein (in blood) less than 30g/L
No clinical manifestations

Smouldering MM
Marrow plasma cells at least 10% and/or M-protein at least 30g/L
No clinical manifestations

Multiple myeloma
Marrow plasma cells over 10% and/or M-protein at least 30g/L
Clinical features of hypercalcemia, renal failure, anemia, bone lesions, infections, plasmacytomas

Waldenstrom's macroglobulinemia
Marrow plasma cells over 10% and M-protein over 30 (IgM)
Clinical features of anemia, bleeding, organomegaly, IgM immunoglobulin

Primary amyloidosis (AL)
Marrow plasma cells less than 10% and M-protein less than 30
Clinical fearures of fatigue, wt loss, purpura, nephrotic syndrome, CHF, neuropathy, orthostatic hypotension, massive hepatomegaly

Links:
Click here for a "medical mystery" from NEJM on panyctopenia
Click here for an excellent review paper on MGUS/myeloma differentiation

Eating disorders- medical complications

Today we discussed the medical complications of eating disorders, which can be devastating and affect any system, with mortality as high as 10% in anorexia and 2% in bulemia. A few points:

Electrolyte/renal abnormalities
-Hypokalemia (may be from vomiting, diuretic abuse, laxative abuse)
-Metabolic alkalosis (volume depletion, diuretics)
-Hyponatremia (diuretics, polydipsia prior to weighings)
-Hypophosphatemia
-Hypomagnesemia
-Chronic kidney disease (may be contributed to by nephrocalcinosis, tubular dysfunction)

Cardiovascular
-Bradycardia (may or may not be secondary to electrolyte abnormalities)
-Cardiomyopathy (potentially reversible)
-Long QT
-Mitral valve prolapse

GI
-Parotic hypertrophy
-Decreased contractility
-Mallory-Weiss teats
-SMA syndrome
-Gallstones

Endocrine
-Amenorrhea
-'Sick euthyroid' syndrome
-Growth retardation
-Hypoglycemia

Skeletal
-Osteopenia/osteoporosis

Hematologic
-Marrow suppression

Neurologic
-Seizures
-Peripheral neuropathy

Dermatologic
-Lanugo hair
-Hair loss
-Yellow/orange skin- hypercarotenema
-Russell sign (callus over knuckles)
-Edema

Refeeding syndrome: When pts become rapidly "anabolic" after prolonged periods of starvation, severe electolyte abnormalities can develop and must be aggressively replaced.
-Hypophosphatemia
-Hypokalemia
-Hypoglycemia
-Edema

Link:

Click here for a NEJM review of anorexia

Click here for a case report of reversible severe cardiomyopathy from anorexia

Status Epilepticus

Today we discussed an approach to status epilepticus and seizures in general.

Defined as continuous or repeated seizures without return to baseline for 20-30min (brain activity; may not have convulsions).
NB- there is a movement to make the time part of this definition much shorter (to 5 minutes)

Most seizures last 1-2 min. You need to intervene if beyond this point. At 20 min, the seizure per se damages the brain (scarring, self-perpetuating as sz focus). Also treat if series of short sz with incomplete recovery in between.

Approach is to treat the seizure AND look for the underlying cause

Acute causes: bleed, stroke, trauma, metabolic (e.g. hypoglycemia, hyponatremia, hypocalcemia, others), infections (esp. CNS), hypoxia, intoxication/drugs (or withdrawal), major organ faiure (uremia, hepatic failure)
Chronic: mass, non-compliance with meds

Complications of sz: aspiration, orthopedic complications, lactic acidosis, rhabdomyolysis

Practical approach:

ABC- clear the airway (do NOT put anything in the pt's mouth to prevent 'tongue biting, etc), roll on side, ensure breathing (apply O2)
Get monitors- Vitals, O2 sat,
IV access
CHECK THE GLUCOSE!, If low, amp of D50, glucagon 1mg IM if no IV
Thiamine 100mg IV (esp. if EtOH, pregnant, cancer pts)
Blood: CBC, lytes, renal, Ca profile, glucose, transaminases, drug levels, tox screen

If no immediately reversible cause (e.g. hypoglycemia), drugs to use acutely:

Benzos- lorazepam IV 12-24h anti-sz effect. Loraz 0.1mg/kg at 1-2mg/min (usually 1-2mg aIV at a time, repeated to max) This will stop 80% of sz.
May give diazepam PR if no IV access. 0.2mg/kg PR x 1 or midazolam 5mg IM x1

Phenytoin (Dilantin) 20mg/kg IV load at 50mg/min (e.g. 1400mg over 30 min in 70kg)
If needed, give further 5-10mg/kg.
A couple of points about phenytoin for status:
Do not mix phenytoin and D5; it crystallizes, which is not very helpful in status epilepticus.
Never give dilantin and dopamine together; can cause profound hypotension for unclear reason

Phenobarbital: Strongly consider intubation here
20mg/kg IV @50-75mg/min. This pt should be in ICU

Others: Propofol infusion, midazolam infusion

Look for underlying- bloodwork, CT, LP if fever.
Mimics of status: myoclonus, rigors, movement disorders, herniation (early)

Link:

Click here for an excellent review of status epilepticus from Chest (yes, a weird place for it to be)

Endocarditis

Today we discussed endocarditis. This is a very important topic to have knowledge of regardless of what area one practices in, both in terms of suspecting and confirming the diagnosis, and proper management. The natural history of untreated endocarditis is 100% mortality. A few points:

Traditional breakdown is by time course; perhaps less relevant today than previously.

Subacute classically presents as a chronic, wasting illness, with fever, wt loss and progressive heart failure and complications as the heart is progressively damaged over weeks to months. Typical organisms are (in order) viridans group streptococci, enterococcus, st. aureus

Acute presents with rapidly progressive valvular destruction over days, often with catastrophic hemodynamic and other complications. Typical organisms are st. aureus, enterococci, viridans group streptococci, HACEK organisms.

Other useful classifications that help with predicting microbiology and complications are native vs. prosthetic valve and R-sided vs. L-sided.

Some physical findings (not exhaustive!)

Signs of valvular involvement or local complications:
-murmurs (esp. AI, MR, TR)
-signs of L or R-sided heart failure
-bradycardia (heart block can occur from paravalvular abscess)

Signs of embolic complications/phenomena and vasculitis
-any focal neurological deficit-peripheral cutaneous signs: Splinter hemorrhages, Osler nodes, Janeway lesions, Roth spots, clubbing, subconjuntival and other mucosal petechiae. Remember to look for these on the feet too
-splenomegaly

Signs of underlying causes
-track marks for IDU
-oral exam for dental hygiene

Diagnosis:
-multiple blood cultures from different sites off antibiotics are KEY to the diagnosis and management

Modified Duke's criteria can be helpful (see link for full details):

Major

-multiple blood cultures consistent or Q-fever serology +ve
-echo consistent (oscillating mass, abscess, dehiscence of prosthesis)
-new murmur

Minor
-predisposing heart condition or IVDU
-fever
-vascular phenomena (emboli, etc as above)
-immunologic phenomena (as above)
-blood cultures not meeting criteria for "major"

Definite: (2 major) or (1 major+3 minor) or (5 minor)
Possible: (1 major and 1 minor) or (3 minor)

ECG- check for new blocks (esp. 1st degree AVB; suggests abscess)

Therapy
General principles- need cidal antibiotic. Generally need minimum 4-6 wks of IV therapy

Indications for valve replacement (NB- surgery is probably under-utilized)
-CHF as a direct consequence
-Severe valvular insufficiency
-Paravalvular abscess
-Embolic phenomena post-initiation of therapy
-Persistently positive cultures or fever despite adequate medical therapy
-Size of vegetation (relative)

Links:

Click here for the complete modified Duke's criteria

Click here for a review article from NEJM