Day #31 - Fever of Unknown Origin

Today we discussed a case of true fever of unknown origin.

Epidemiologic Criteria:

• Fever x 3 weeks (38.3)
• Failure to find cause despite appropriate initial outpatient/inpatient investigations

Causes:

• Majority unknown
• Then infection (most commonly TB or occult abscesses), inflammatory, malignancy, other

Diagnostic tests (beyond initial):

• CT abdomen to look for abscess, lymphadenopathy, other pathology. Yield ~20%
  
• Bone scan (insensitive, but specific with good + LR)
• Liver biopsy -- regardless of hepatomegaly or LFT abnormalities has yield ~15%
• Temporal artery biopsy in the elderly -- yield ~ 15%
• Leg dopplers -- yield 2-6%
• Bone marrow biopsy-- in those with cytopenias or compatable syndromes. Yield ~1%

Day #30 - Transient Ischemic Attack

Today's case was an acute stoke with rapidly resolving deficits. We discussed localization of infarcts and localized this case to the midbrain based on the constellation of deficits.

The following images are helpful in reviewing the sensory and motor pathways.



In patients with TIAs there is a definite risk of ~10% in the next 90 days of having a stroke. Studies suggest that 1/2 of this risk happens in the first 3-7 days. Consequently, a TIA should be thought of as a medical emergency warranting risk factor modification and assessment for treatable cause (i.e. atrial fibrillation, >70% ipsilateral carotid stenosis). However, not all transient neurological symptoms are TIAs! We need some means of selecting which patients are most likely to actually have a stroke so we can focus our efforts on them.

Several attempts have been made to help determine which patients with TIA are most likely to have a stroke. The one I like is the ABCD2 score.

A - Age Greater than 60 == 1 point
B - BP >140 in ER == 1 point
C - Clinical Features: Weakness == 2 points, Speech problem == 1 point, other == 0
D - Duration: >1hr ==2 points, 15-60mins = 1 point, <15 mins = 0 points
D - Diabetes == 1 point

Low Risk = 0-3 points -- 1.0% had stroke in 2d, 1.2% in 7d, 3.1% in 90d
Medium Risk = 4-6 -- 4.1% in 2 d, 5.9 in 7d, 9.8% in 90d
High risk = Greater than 6 -- 8.1% in 2d, 12% in 7d, 18% in 90d

Consider that crescendo TIA is a different story and this model does not apply to patients with crescendo TIAs.

In general low risk patients can be treated as outpatients with risk factor modification and investigations.

Medium risk patients probably can be treated with expedited investigations and risk factor modification. This will depend on the clinical context. For example a 40 year-old patient with 3 hours of objective weakness would score 4, but probably should be more urgently investigated.

High risk patients should probably be admitted for urgent investigations and for monitoring for indications for acute thrombolysis should stroke occur.

Day #29 - Demand Ischemia

Today we talked about a case of a young man who essentially presented with status epilepticus and was found to have some non-specific ECG changes, a CXR compatible with CHF though without evidence of CHF on clinical exam, and an elevated cardiac troponin.

The discussent, a cardiologist, facilitated a good discussion on the approach to a patient with seizures including considering that what was labelled "seizure" may, in some patients with underlying cardiac dysrthmias or ischemic/structural heart disease be a presentation of primary cardiac abnormalities.

In this patient, who subsequently turned out to have a normal baseline ECG and a normal 2D echo and who will go on to angiography, the suspicion is that this troponin increase was caused by severe myocardial demand during the status epilepticus. The combination of catecholamine surge, increased muscle tone leading to increased afterload, and tachycardia presumably led to sub-endocardial ischemia.

There are conflicting case reports about whether seizures themselves can lead to troponin increases with one small patient series saying no, and several single patient case reports saying yes. I think the take home message from this is that you can't write off significantly elevated troponins as being entirely due to the seizure.

We spent some time discussing stress-induced cardiomyopathy or apical ballooning syndrome. There are some case reports of status epilepticus causing this syndrome (in one of these cases the troponin was elevated to 10!).

Also, if you haven't done so already, I would suggest you review the blog on seizures/status epilepticus.

Day #28 - Thrombocytopenia

Today we talked about a case of an elderly man who presented with isolated acute, relatively asymptomatic, severe thrombocytopenia.

We discussed an approach to the differential diagnosis of thrombocytopenia:

• Decreased production: i.e. myelodysplasia, leukemia/lymphoma, other infiltrative malignancy (i.e. breast cancer), substrate deficiency (B12/folate), toxins (ETOH, methotrexate, chemo), infections (measles, mumps, rubella, EBV),
  
• Sequestration in the spleen
  
• Increased destruction:
  
  • Immune mediated: collagen vascular disease including SLE and APLA, viral - HIV/HBV/HCV/EBV/CMV, Idiopathic Thrombocytopenia Purpura, drug related - i.e. vancomycin/septra/quinine, heparin induced thrombocytopenia (HIT), post-transfusion purpura
    
  • Non-immune mediated: DIC, TTP/HUS, HELLP syndrome, sepsis
    
• Congenital/Gestational

We used this differential to focus our history and physical exam, then used that information recursively to make come up with an investigation plan.

After reviewing the lab tests including bone marrow biopsy we decided that the most likely diagnosis in today's case was ITP and then touched upon treatment. There are guidelines on treatment published but these date back to 1997.

NB: Patients should be immunized against pneumococcus, haemophilus, and neiserria species on diagnosis in case splenectomy is required.

Treatment for ITP

1. When: Risk of bleeding complications is greater than the risk of treatment
   
   • Is there severe or life threatening bleeding ==> TREAT
   • Is the risk of bleeding high because PLT <10> TREAT
   • Is the PLT count <30-50?
     
     • Bleeding? ==> TREAT
     • Asymptomatic but risk of bleeding due to lifestyle or other conditions ==> consider TREATING, discuss with patient
       
   • Is the PLT count >30-50 ==> Observe
2. How:
   
   • Steroids:
     
     • Prednisone 1mg/kg PO OD -- should work within 1-2 weeks. If not consider other method. Taper over 4-6 weeks after PLT count normalized
     • Dexamethasone 40mg PO OD x 4 days -- repeat in 14-28d as needed to complete 4-8 "cycles". Head to head trial with prednisone is underway
     • Pulse solumedrol -- small studies suggest benefit, large studies pending
       
   • IVIG -- 1g/kg/day x 1-2 days. Response in a few days, duration several weeks
   • Second line therapy:|
     
     • Splenectomy -- 4-6 weeks of treatment should happen first to allow for spontaneous remission. Will induce remission in ~ 65%. Risk of overwhelming post splenectomy infection (OPSI) of ~ 1/1000 per year.
     • Rituximab -- insufficient evidence to recommend. Use limited to patients with an unacceptably high risk from splenectomy
   • Refractory ITP (Plt <50,> 3 months, failed splenectomy)
     
     • Specialty consultation required. Consider observation, chronic steroids, rituximab, cyclophosphamide, other immunosuppressives/modulatories
     
     

Meningitis

The meningitis lecture from today is available here.

Day #25 - Adrenal Insufficiency

Today we talked about a case of a woman with a history of chronic steroid use who presented with refractory hypotension and hypoglycemia in the context of a systemic infection. The team were highly suspicious that this represented adrenal insufficiency in the context of a stressor. I wanted to touch upon how one can make the laboratory diagnosis of adrenal insufficiency.

The first step is to obtain morning (8AM) measurements of cortisol and ACTH.

• If the cotisol is below 80nmol/L the diagnosis is confirmed. If the ACTH is high, this suggests primary adrenal insufficiency, if the ACTH is inadequate this suggests secondary or tertiary adrenal insufficiency
  
• If the cortisol is above 500nmol/L the diagnosis is essentially excluded.
• If the cortisol is between 80-500, dynamic testing is required

The downside is that ACTH takes a long time to come back, and often you don't want to wait until 8am to make the diagnosis.

Dynamic testing (can happen at any time of day when the lab is open):
Obtain baseline cortisol measurement.
Then administer cosyntropin 250mcg IV
Then obtain cortisol measurements at 30 and 60 minutes post injection

If the cortisol increases to >550nmol/L then primary adrenal insufficiency is excluded and probably secondary as well -- although not definitively. If you have a high index of suspicion for secondary or tertiary adrenal insufficiency you should probably consult an endocrinologist as you will need specialized testing (i.e. CRH stimulation test, insulin induced hypogylcemia test, metrapyrone test)

In suspected adrenal crisis, you should obtain a STAT cortisol and ACTH measurement then start treatment with steroids and IV saline. Dexamethasone is preferable because it won't be picked up on the cortisol assay and consequently you can continue treatment while working up the patient. Remember that dexamethasone can suppress ACTH release, and so you will need to do dynamic testing unless the baseline studies are diagnostic.

Day #24 - Colitis

Today we discussed a gay male with fever, abdominal cramping, tenesmus and bloody diarrhea. The discussant made a very important point -- the clinical context and history are very important in making the diagnosis in acute colitis.

Before making the diagnosis of IBD one should exclude infections by history and special tests. Infections can mimic IBD clinically, radiographically, and endoscopically.

I wanted to talk about the differential diagnosis of bloody diarrhea with fever.

Differential Diagnosis

Infectious

• Enteroinvasive infection: Salmonella, Shigella, Campylobacter, E. Coli 0157:H7 (associated with HUS, frequently afebrile), Clostridium difficile, Klebsiella oxytoca
  
• Associated with receptive anal intercourse: HSV proctitis, gonorrhea, chlamydia (L serovar - AKA LGV/lymphogranuloma venerium), syphilis
  
• Associated with oral-anal practices or colonic irrigation: intestinal amebiasis
• More chronic, associated with the terminal illeum: intestinal tuberculosis
• Immunosuppressed patients: CMV colitis
  

Inflammatory

• Ulcerative colitis/Crohn's disease
  

Ischemic Colitis

There is also a good case of a patient with fever and diarrhea in the NEJM available here.

Physical Exam - Splenomegaly

"Does this Patient Have Splenomegaly?"

What is splenomegaly? Normal spleen is 12x7x3. Radiographically splenomegaly can be defined as 13cm cephalocaudad on ultrasound

Inspection:

• Look for left upper quadrant masses (low sensitivity)

Percussion:

• Castell's Sign (in Traube's Space):
  The patient is supine. You percuss in the lowest intercostal space in the left-anterior axillary line in full expiration and inspiration. Splenomegaly is suggested when the percussion is dull or becomes dull on inspiration.
  SENSITIVITY 60-85% SPECIFICITY 72-82%
• Nixon's Method:
  Place the patient in the right lateral decubitus position. Initiate percussion half-way along the costal margin and percuss cephalad in a line perpendicular to the costal margin. Dullness of >8cm suggests splenomegaly.
  SENSITIVITY 60% SPECIFICITY 95%

Palpation:

• One-handed technique: Patient is supine, you palpate with the tips of your fingers starting in the right lower quadrant and moving towards the left upper quadrant in small (~2cm) incriments. The patient takes slow deep breaths at each point and you feel for a descending spleen
• "Middleton's Manouver"/Splenic Hook: The patient lies flat with their left hand under their left CVA. The examiner, standing on the left of the patient, curls the fingers of both hands under the left costal margin and the patient is asked to take a deep breath.
• To distinguish the spleen from other LUQ organs one can feel for the splenic notch. Also, one should not be able to palpate superiorly to the spleen. The spleen should also move with respiration while large kidneys will not.
  SENSITIVITY: 60-70% SPECIFICITY: >90%

Auscultation:

• Listen for splenic rub (suggests infarction), splenic artery bruit (suggests congestive splenomegaly). These signs were not evaluated in this article.
  

Who should I examine for splenomegaly in? In patients with a pre-test probablility of splenomegaly of less than 10%, the likelihood of the physicial exam being helpful to exclude or rule in splenomegaly is quite low. That is, a negative exam could be a false negative, a positive exam a false positive.

Consequently, the physical exam should be performed in those with a pre-test probability of >10%.

How do I interpret my exam? In patients with no dullness to percussion, you should move on to ultrasound if the clinical question remains significantly important. Palpation will not add useful information because of its poor sensitivity.

In patients with dullness but a non-palpable spleen ultrasound/imaging should be performed to definitively confirm/exclude.

In patients with dullness to percussion and a palpable spleen, the diagnosis is established.

Day #23 - Rhabdomyolysis

Today the discussant provided a broad and comprehensive approach to bilateral leg weakness and using the clinical clues of bilateral leg pain (thigh/calf), inabilty to ambulate, and pseudohematuria we arrived at the diagnosis of rhabdomyolysis.

Causes of Rhabdomyolysis Include:

1) Toxins

• Direct myotoxins: statins (particularly with fibrates), corticosteroids, some antifungals/antibiotics
  
• Indirect myotoxins: alcohol, benzodiazepines, cocaine, ecstasy, methamphetamines, LSD, paralytic agents, carbon monoxide
  

2) "Trauma"

• Prolonged immobility, crush, electrocution
• Post exertional: marathon, overexertion in the "unfit"
  
• Heat stroke, Neuroleptic malignant syndrome, malignant hyperthermia

3) Metabolic

• Hyper/hyponatremia, hypokalemia, hypophosphatemia, hypocalcemia, hyper/hypothyroid
• Genetic abnormalities in lipid, carbohydrate or purine metabolism
  

4) Inflammatory/Infectious (viral including HIV, parasitic, other)

Treatment of Rhabdomyolisis:

• Remove precipitant if possible
• Fluids, Fluids, Fluids -- Litres of Normal Saline or other fluid will be required, usually at rates up to 250-500cc/hr after initial boluses. The goal is to correct any existing pre-renal azotemia, see the CK decrease to <1,000>
• Watch for electrolyte abnormalities and correct them! In particular life threatening hyperkalemia can occur.
  
• Watch for compartment syndrome

Though there are biologically plausible reasons, there is an absolute paucity of evidence in favor of urine alkalinization. It is likely that adequate volume replacement is much more important than alkalinization. There are several caveats to attempting to alkalinize the urine including:

• Development of significant metabolic alkalosis (perhaps severe)
• Potential for hypokalemia and hypocalcemia
  

If you are going to try to alkalinize the urine you should use 3AMPS of HCO3 in 850cc D5W to make a solution that is relatively isotonic to normal saline and then run it at adequate rates to volume rescucitate the patient. Your goal is to make the urine alkaline (pH >=7) while keeping the serum pH < 7.6 (ideally <7.55).

There is also a paucity of evidence for forced diuresis with mannitol or furosemide and I would not recommend it unless you need to because of volume overload. In that case, perhaps early hemodialysis would be superior.

Day #22 - Advanced Cirrhosis

Today we had an expert hepatologist come to talk with us about a case of a patient with cirrhosis, chronic hepatitis B, and hepatocellular carcinoma. Many things were discussed but I wanted to touch upon a few regarding the complications of chronic liver disease and treatment thereof.

The discussant divided the complications into those related to portal hypertension and those not related to portal hypertension. This is a useful framework.

Remember, if you can stop the process that is damaging the liver (ETOH, HBV, HCV) you may be able to make a big difference in patient outcomes.

Portal HTN related:

Varices - Esophogeal, Gastric

• Avoidance (if possible) of NSAIDs
  
• Surveilance OGD q2 years if no varices, q1 year if low grade varices, more frequently if high grade varices or bleeding
• Endoscopic therapy (banding): For those with high grade varices or those who have bled (may not be superior to pharmacotherapy).
  
• Pharmacotherapy: non-selective beta-blockers +/- isosorbide mononitrate for patients with known varices and those who have bled
• Combination of both endoscopic therapy and pharmacotherapy may be the best for primary and secondary prophylaxis

Ascites

• Fluid and Salt Restriction
• Diuretics: spironolactone and furosemide (oral) in dose ratio of 100:40 titrated to effect. Goal is to increase 24h sodium excretion above intake
• Therapeutic Paracentesis
• TIPS

SBP - See Day #18

Splenomegaly and hypersplenism

Hepatorenal or Hepatopulmonary syndromes

Non-Portal Hypertension Related:

Encephalopathy

• Avoidance of precipitating medications (benzos, narcotics) and foods (e.g. high protein load)
• Recognizing precipitants -- GI bleeding, infection, renal failure, hypokalemia
• Protein restriction
  
• Lactulose -- Often used with little evidence
• Antibiotics -- RIFAMIXIN

Synthetic Dysfunction -- Supportive care

Hepatoma:

• Risk Factors:
  HBV, HCV, FHx, Toxin Exposure, (?smoking)
• Screening: Ultrasound +/- AFP on an annual basis for those with high risk features
• Early treatment

---

We also talked about the Child-Pugh and MELD scores as prognostic aids and tools for selecting patients for transplantation referral.

Status Epilepticus

We had a great noon rounds session today on status epilepticus. A pharmacological management strategy (taken from that paper) is shown in the figure below:



You should note that a later publication suggests that initially patients should treated with IV lorazepam and phenytoin up-front and then if seizures continue after 10 minutes they suggest you should move on to anesthesia and intubation citing a low response rate to second line agents (e.g. phenytoin, phenobarbitol, repeat lorazepam).

Also remember:

1) Secure the airway if required, give oxygen, and obtain IV access
2) Thiamine +D50 if any chance seizure is hypoglycemic in origin
3) Treatment of hyperthermia (T>40) with active cooling
4) Search for cause of seizure as appropriate.

Day #21 - Hypercalcemia

Today we presented a case of altered mental status related to hypercalcemia. The discussant talked about the common causes of hypercalcemia as well as touched upon management. Some relevant take home messages include:

Symptoms of Hypercalcemia: Think "STONES, MOANS, GROANS, BONES, mental OVERTONES."

Causes of Hypercalcemia:

1. Hyperparathyroidism (primary, secondary, tertiary)
2. Malignancy Associated due to:
   (a) PTHrP -- Squamous cancers of lung/throat, Breast, RCC, GU, other
   (b) Bone destruction/Local Osteoclast Activation -- Breast, Myeloma
   (c) Hypervitaminosis D -- Lymphoma, Breast (rare)
   
3. Hypervitaminosis D due to sarcoid, iatrogenic
4. Iatrogenic: Calcium supplements, thiazide diuretics, lithium, etc.
   
5. Prolonged immobility
6. Other endocrine: Hyperthyroidism, Acromegaly, Adrenal Insufficiency
7. Other

NB: The malignancy is usually clinically apparent!

Treatment:

• If possible, remove the precipitant and correct any hypophosphatemia.
  
• Saline replacement of ECF volume then maintenance of euvolemia. Often requires several litres of IV fluid to correct for the profound ECF contraction. Hydration alone will often bring the calcium down significantly
  Consider the addition of FUROSEMIDE if you've made them hypervolemic.
  
• IV Bisphosphonates: Pamidronate 45-90mg IV over 90 minutes. Will work within 48-72 hours. Watch for post treatment hypocalcemia
• If still unsuccessful:
  (a) ensure you are not behind in hydration!!!
  (b) can add calcitonin 4-8IU/kg SC q12h
  (c) consider adding PREDNISONE 60mg PO OD x 10d if suspect the problem is increased 1,25-OH vitamin D
  (d) Consider dialysis

I have only had to resort to measures beyond bisphosphonates once and in that case (lymphoma associated) there was a great (initial) response to prednisone.

A great review article on hypercalcemia and malignancy is here.

TGH "Case of the Week" July 14-18, 2008

30F with known HIV (CD4 unknown, not on treatment) presents with acute onset fever, chills, rigors, and cough with sputum. On exam she is febrile, tachycardic, hypotensive, hypoxemic on room air requiring hi-flow oxygen to maintain saturations >90% and in moderate respiratory distress.

The chest x-ray is taken and appears below:



Questions:

1) What is the most likely microbiological diagnosis?
2) What is the differential diagnosis?
3) What tests would you order to make your diagnosis?
4) What empiric treatment would you initiate in the ED?

BONUS: What "management strategy" would you employ in the ED and what journal was the study published in?

Thank you to the people who submitted answers. The "contest" is closed for this week. The winner will be notified in person.

"Answers"

1) The most likely etiologic agent to cause a lobar pneumonia in a patient with HIV is still streptococcus pneumoniae. In fact, patients with HIV are at an increased risk of getting pneumococcal infections and should all be vaccinated with the polysaccharide vaccine.

2) The differential diagnosis includes lobar pneumonia with the other organisms of community acquired pneumonia including haemophilus influenzae, moraxella cattharalis, and Staphylococcus aureus. Of particular concern in a patient who is rapidly deteriorating is community acquired MRSA necrotizing pneumonia.

Other causes would include Legionella pneumophillia and if risk factors such as underlying structural lung disease enteric gram negative organisms.

Upper lobe pneumonia should prompt concern for tuberculosis, although in this case the acquity and sepsis-syndrome argue more strongly in favor of bacterial pneumonia.

PCP tends not to be lobar and consolidative and the classic x-ray appearance looks more like bilateral peri-hilar interstitial infiltrates.

Fungal pneumonias like cryptococcal pneumonia, blastomycosis, invasive aspergillosis are unlikely and would not generally have this radiographic appearance and acute presentation.

3) Blood cultures should be sent ASAP (ideally before antibiotics) as they may be positive in up to 25% of cases of pneumococcal pneumonia. Sputum cultures should also be sent for conventional culture, legionella culture and TB culture. I would not recommend sputum for PCP in this case.

Urinary antigen detection for pneumococcal antigen is used in some centres (not here). Urinary antigen testing for legionella can help make this diagnosis.

CD4 testing in acute illness may not be helpful as the acute illness could cause a decrease in the counts; however, it would not be unreasonable as if the CD4 count was >200 rare causes are much more unlikely.

4) In a septic patient with community acquired pneumonia you need to cover broadly for the most likely pathogens. There are many ways to do this and in some cases what you choose will depend on recent antibiotic exposure.

In this case a combination of VANCOMYCIN 1gIV q12h and LEVOFLOXACIN 750mg IV/PO q24h would be appropriate. This would cover MRSA and quinolone resistant pneumococcus, the usual pathogens including the majority of pneumococcus, unusual pathogens like legionella, and many enteric gram negatives.

BONUS: The management strategy to be employed is "Early Goal Directed Therapy in Sepsis"

Day #18 - Cirrhosis

Today's case was of a 52 year-old man who presented with new diagnoses of cirrhosis with ascites, portal hypertension and probable variceal bleed who also had a new diagnosis of diabetes mellitus. The discussant showed us, although in his own uniquely tangential way, the type of clinical reasoning that great physicians use in arriving at a diagnosis.

There are a number of valuable teaching points today:

1) Ascites:

Etiology

• Elevated Hydrostatic Pressure --> CHF, constrictive pericarditis, Budd-Chiari, cirrhosis, IVC occlusion
• Decreased oncotic pressure --> malnutrition, nephrotic syndrome, protein losing enteropathy, cirrhosis/liver failure
• Increased fluid production in peritoneum --> infection (TB), neoplasm

Diagnosis on History/Exam
History

• Increased abdominal girth and ankle swelling are the most sensitive (greater than 85%)
• Past history of hepatitis or cancer are the most specific (greater than 85%)

Exam

• Not likely if no bulging flanks, no flank dullness and no shifting dullness
  
• Likely if fluid wave, shifting dullness, and peripheral edema (LR+3.8/-0.2)

2) Special Tests:

The team today also mentioned that they had performed a paracentesis in order to evaluate the ascites. This is important as paracentesis can:

1. Provide diagnostic clues
2. Exclude SBP

The Serum Albumin-Ascites Gradient (SAAG) is a valuable tool in deciding if the ascites is due to portal hypertension. SAAG = Serum albumin - Ascites Albumin. If <11 style="font-style: italic;">It should also be prevented in cirrhotic patients post GI bleed using TMP/SMX 1DS PO BID x 7d or CIPROFLOXACIN 500mg PO BID x 7d

The diagnosis can be made on the paracentesis:

• PMN >250 (LR + 6 LR - 0.2)
• WBC >1000 (LR + 9)
• Inoculation of blood culture bottles (fill them with required volume) can improve yield of the C/S

NB: In most cases, you do not need to use FFP/Platelets pre paracentesis.

Initial treatment is with CEFTRIAXONE 2g IV q24h with coverage narrowed to the culture data. You need only treat for 5 days.

Patients should get 1.5g/kg of 25% albumin within 6h then 1g/kg on day 3.

NB: Think of missed perforation if multiple organisms grow in the culture or if the WBC count in the fluid is much greater than 1000.

Digoxin Toxicity

Who gets digoxin toxicity?

• Significant interactions with P450 pathway can lead to accumulation. A thorough drug history including recent discontinuations is important.
  
• Toxicity can occur in patients on stable doses who develop renal failure because of accumulation
  
• Toxicity is increased in older patients and those with hypokalemia, hypernatremia, hypomagnesemia, hypercalcemia

Symptoms:

• Blurred vision, coloured haloes
• Confusion, fatigue, delerium, hallucinosis
  
• anorexia, nausea, vomitting, diarrhea, abdominal pain

ECG/Conduction abnormalities:

• Bradycardia
• Ventricular ectopy (PVCs, bigeminy, small runs of VT)
• AV block - 1st, 2nd, 3rd degree
  
• atrial tachcardias with 2:1, 3:2, 4:1, 6:1 or sometimes variable AV block
• Accelerated Junctional Rhythms (particularly with HR >60)
  
• VT/VF
  

Levels (measure 6-12h post last dose):

• Goal levels in heart failure are 0.65-1.1mmol/L
  
• Normal levels usually less than 2.6mmol/L; however, hypokalemia can lead to toxicity despite lower levels
• Levels greater than 3.9mmol/L are usually symptomatic

Treatment:

• Supportive care
• Symptomatic bradycardias usually respond to atropine
• Attempt to avoid pacing if possible (irritible myocardium)
• Attempt to avoid beta-agonists (irritible myocardium)
  
• Treat hypokalemia and hypomagnesemia
• Cautious treatment of hyperkalemia -- avoid calcium salts

"Digibind" - F(ab) fragments of engineered antibodies designed to bind to drug. For use in:

• Hemodynamically unstable
  
• Life threatening arrythmia
• Digoxin toxic rhytym with elevated digoxin level
  
• "Severe bradycardia"
• K+ >5 in acute ingestion
• dig level greater than 13 mmol/L or ingestion more than 10mg

Digibind will make further measurements of dig level inaccurate for >1 week. Ensure you dose it appropriately --> digoxin level x weight /100 = approximate # of vials.

Day #17 - Renal Failure

Today we talked about the approach to renal failure. It is easiest to conceptualize etiology and treatment using the pre-renal, renal, and post-renal framework which I will summarize. I have also included some great articles about a few of these conditions below.

Pre-Renal:

• Hypotension
• Hypovolemia
• Decreased ECF states - CHF, cirrhosis, bilateral renal artery stenosis

Renal:

• TTP/HUS
  
• Acute Tubular Necrosis (ATN) -- Toxic/Ischemic injury (contrast, aminoglycosides, prolonged hypotension)
  
• Acute Interstitial Nephritis (AIN) -- Drugs (i.e. penicillins, NSAIDS)
  Don't rely on urine eosinophils to make this diagnosis
  
• Glomerulonephritis (includes renal vasculitis)
  
• Nephrotic Syndrome
  

Post-Renal:

• Obstructing stones/masses
• Urinary outflow obstruction -- i.e. prostate, neurogenic bladder
  

Treatment:
Pre-Renal --> Treat hypotension and hypovolemia. Treat CHF.
Post-Renal --> Relieve the obstruction. Watch for post-obstructive diuresis and treat it appropriately.

Renal --> Stop the precipitant if there is one. Treatment is otherwise context dependent.

---

FYI the article on the "digoxin soup" is here.

Day #16 - Hepatitis

Today we talked about a patient with acute hepatitis with transaminases ~1000 in a hepatocellular pattern.

There are a limited number of causes of such an acute hepatitis:

• Viral hepatitis (Hep A, Hep B, Hep C, HSV/CMV)
• Toxic Hepatitis --> tylenol, toxic mushrooms, severe ETOH (AST/ALT rarely above the 100's), other
• Stone in the common bile duct
• Ischemic Hepatitis/Shock Liver/Acute R-sided CHF
  
• Budd-Chiari Syndrome
• Autoimmune, Wilson's, Pregnancy, Aggressively infiltrating cancer
  

From Wallach, Interpretation of diagnositic tests (2006):
"Rapid rise of AST and ALT to [>600] followed by sharp fall in 12-72h is said to be typical of acute bile duct obstruction due to a stone"

... The caveat is that if you have a fulminant hepatitis the AST/ALT may decrease because there are no hepatocytes left to die. So it is all in the clinical context.

The discussant was suspicious that this was a case of a biliary stone despite the stone not being seen on ultrasound. This raises an important point. We often rely on imaging to help make the diagnosis; however, we need to be mindful that even the best imaging tests can be falsely negative. I am reminded of the axiom "a rare presentation of a common disease is most likely than a common presentation of a rare disease"

The team also very astutely decided to treat for potential paracetamol/acetaminophen toxicity based on the patient's medication history. There is a great article in NEJM which talks about the treatment of acetaminophen poisoning.

Day #15 - Acute Polyarthritis

Today we discussed a case of a 32 year-old woman with acute/sub-acute onset polyarthritis. The discussant worked us through the differential diagnosis and how to use the history, physical and investigations to arrive at a more definitive diagnosis.

In making a diagnosis we use clinical and laboratory factors. There are diagnostic criteria for each condition which are helpful epidemiologically but can also point out some of the key features of the illness. Recognize that not having all the criteria does not necessisarily mean the patient doesn't have the disease! Just not from a formal epidemiological point of view.

For RA one needs 4/7 of the following (ACR Criteria circa 1980):

1. Morning stiffness lasting >=1 hour
2. 3 or more joints with effusions as examined by a physician. Most commonly wrists, knees, MCPs, PIPs, knee, ankle, MTP
3. Involvement of joints of the hand (wrist, MCP, PIP)
4. Symmetric involvement of similar joints on both sides of the body
5. Rheumatoid nodules
6. Rheumatoid Factor
7. Typical radiographic changes

NB: 1-4 need to be present for >=6 weeks

For SLE one needs 4/11 which I like the mnemonic MD-SOAP-N-HAIR:

1. M - malar rash
2. D - discoid rash
3. S - serositis (pleuritis, paricarditis, rarely peritonitis)
4. O - oral/nasal ulcerations (typically painless, but can be painful)
5. A - Arthritis - symmetric, non-erosive polyarthritis usually involving hands
6. P - Photosensitivity
7. N - Neurologic - seizures or psychois
8. H - Hematologic - Hemolytic anemia or leuko/lymphopenia (unexplained) or thrombocytopenia (unexplained) and persistent
9. A - ANA positive
10. I - Immunologic - Anti-DSDNA, Anti-Sm, Antiphospholipid antibodies
11. R - Renal - Proteinuria or active sediment (casts)
    

In this case, it was rheumatoid arthritis and we then discussed initiating management. The key is to remember that DMARDs take time to work and you will need to use something (NSAIDs if mild, PREDNISONE if moderate-severe) until the DMARDs work.

I also found a great site today, www.rheumatology.org, which has a number of good teaching materials under "Students and Residents".

Day #14 - Hyponatremia

Today a case of severe hyponatremia was presented. The discussant clearly illustrated an approach to hyponatremia which allows one to characterize the causes and therefore make a plan for management. Take home points include:

Severe, symptomatic hyponatremia is a life threatening emergency! If patients are obtunded, seizing, or at imminent risk of herniating due to increased intracranial pressure you should aim to correct the serum sodium by approximately 5mmol in as little as 30 mins. This is done with intravenous 3% or 5% sodium chloride, and if you are going this route you had better be sure of exactly what you are doing, or consult someone who is! Once this is done, if they are symptomatically improved, you then need to correct more slowly.

Asymptomatic hyponatremia is less life threatening. In fact, the doctor may be the most dangerous thing the patient encounters. If one corrects the sodium too quickly the patient is at risk of central pontine myelinolysis which can lead to severe morbidity. Goal is to correct 6-8mmol/24h.

In general the approach to correcting the sodium is dependent on whether the patient is hypovolemic, euvolemic, or hypervolemic.

• Hypovolemic -- i.e. dehydration repleted with hypotonic fluid, diuretics, GI losses, adrenal insufficiency
  Replete volume if hemodynamically unstable. Can use fluid that is isotonic to their serum if there is a concern about changing the sodium with rescucitation. Watch for free-water diuresis when euvolemic as the stimulus for ADH may be the hypovolemia. In cases where the initial sodium is less than 120 consider giving a small dose of DDAVP (2-4mg IV q12h) to prevent this massive free-water diuresis causing rapid over correction.
  
• Euvolemic -- SIADH, hypothryoidism, adrenal insufficiency, psychogenic polydipsia
  Try and stop the stimulis for the SIADH. Fluid restriction is usually sufficient to correct the hyponatremia. If not working and patient adhering to fluid restriction, can restrict further or add low dose loop diuretic like furosemide.
• Hypervolemic -- Heart failure, nephrotic syndrome, cirrhosis
  Fluid restriction plus loop diuretics.
  

Day #11 - Upper GI Bleed

Today's case was of an acute upper GI bleed.

The essentials on management include:

• Attend to airway and breathing first -- if you need to intubate to protect the airway in massive hematemesis or to facilitate safe endoscopy you should do so
  
• Circulation:
  1) Obtain good peripheral access -- '2 large bore' peripheral IVs (16-18ga), one in each arm. A 3-lumen central line is not as effective as two good peripheral lines -- if central access is required a CORDIS can be inserted centrally and can be used to deliver blood and fluids quickly.
  2) Volume resuscitate the hypotensive patient with crystalloid and blood (ideally cross matched, in an emergency can use un-matched but best not to)
  3) Use vasopressors as required while rescucitating but avoid VASOPRESSIN.
  
• Stop the bleeding:
  1) Reverse coagulopathies -- FFP for INR >1.5, Platelets if <50-100
  2) High dose proton pump inhibitor --> can reduce need for transfusion and downgrade gastroscopy findings
  3) Octreotide for suspected/known variceal bleed
  4) Arrange for urgent endoscopy if appropriate
  5) In variceal bleed where endoscopy will be delayed can use local tamponade with Blakemore or Linton tubes (ICU)
• In "massive" transfusion remember:
  1) Transfuse ~ 1u platelets per 5 of blood
  2) Transfuse ~2-4u FFP and ~10 of cryoprecipitate per 10 of blood
  3) Replete calcium because citrate in blood with chelate it and calcium is required for coagulation
  4) Watch for hypothermia (warm the blood if possible) and hyperkalemia (blood has a high K load)
• Prophylaxis for SBP in cirrhosis --> ciprofloxacin or ceftriaxone IV

Regarding the steroid issue -- steroids are associated with a RR of 2.4 for gastric bleeding which increases to 4 in the context of low dose NSAIDs and 12.7 in the context of high dose NSAIDs.

Day #10 - Alcohol Withdrawl

Today's case involved the diagnosis and management of the various alcohol withdrawal syndromes. The take home points include:

Alcohol withdrawal can have several phases which begin after cessation of regular alcohol consumption. These do not necessarily all occur, or occur in order but generally speaking:

• Seizures -- generalized, tonic-clonic, generally no focality, lasting short duration and with short period of post-ictal confusion. Can have up to five in rapid succession. Tend to occur 6-48h post ETOH and can occur with ETOH still on board. Treatment is supportive. Benzodiazepines like lorazepam or diazepam can prophylax against further seizures and other symptoms of alcohol withdrawal
• Autonomic symptoms -- tremor, flushing/diaphoreis, agitation/anxiety, tachycardia, mild hypertension. Treatment is supportive with benzodiazepines given either as an up-front load until drowsy or on a prn basis with the CIWA protocol.
• Hallucinosis -- Development of visual (often frightening images/faces/animals) hallucinations and tactile hallucinations
• Delirium Tremens -- Autonomic instability, agitation, fluctuating level of consciousness/delirium. Need to exclude other causes of delirium.

We also talked about some of the hematological consequences of ETOH abuse including:

• macrocytosis with or without overt anemia
• thrombocytopenia -- can become thrombocytosis if ETOH stopped as platelets will "rebound"
  
• pan cytopenia with con-commitment folate or B12 deficiency

Other important nutritional deficiencies include:

• thiamine -- Wernike's encephalopathy think WACO (W=Wernike A=ataxia C=confusion O=opthalmopalegia) where the opthalmopalegia is most commonly 6th nerve (bilateral or unilateral). Korsikoff's encephalopathy -- anterograde amnesia, confabulation
• B6 -- pernicious beri-beri, alcoholic neuropathy
• folate/B12
• magnesium

Day #9 - I see two people....

Great case today about headache and diplopia. My feeling about the case was that this represented a lacunar stroke that just wasn't seen on the MRI. Treatment would involve modification of the vascular risk factors.

The discussant very methodically went over an approach to diplopia. I think his anatomical approach was excellent:

• Neurological -- i.e. ischemia/vasculitis, demyelination, tumour (including leptomenegeal), infection (TB, syphilis, listeria, lyme), toxic/metabolic (alcohol/wernike's)
  
• NMJ - mysesthenia and other myesthenic syndromes
  
• Muscular/Structural - Graves, masses in the muscles, muscular impingement
  
• Opthomologic -- monocular diplopia -- think corneal or lens problem
  

In this case I think it was important to think about temporal arteritis because of the diplopia and headache. Temporal arteritis will lead to blindness if not diagnosed and treated. Clues on history and physical include:

• Diplopia
• Jaw/Tongue claudication
• Temporal artery beading and tenderness

Excluding subarachnoid hemorrhage is important given the right clinical context (i.e. in the context of the characteristic thunderclap headache). A normal CT scan and negative lumbar puncture are sufficient to exclude with high sensitivity and low negative likelihood ratio provided there are no gross neurological deficits.

Also, remember syphilis is the 'great mimicker' and in "young" patients with stroke/stroke-like syndromes one should think about excluding this diagnosis.

Poisonings and Overdose

The noon rounds today was particularly well received. Those of you who would like a copy of his talk can email me and I will arrange to send it to you.

I would also suggest that you work through this case which illustrates a number of important things.

Day #8 - The Bacteremia that Won't Go Away

Today the discussant described evaluating for exit site and tunnel infections and differentiated these from catheter tip infections with bacteremia. We then talked about diagnosis and management of line-related infections focussing of a few specific pathogens. Here are a few take-away points:

One should obtain paired, labeled blood cultures from the periphery and line in question. The differential time to positivity can help determine whether the line is the source of the infection as follows

• Line and blood simultaneously positive suggests that the line is not the focus
• Line positive 2 hours before periphery suggests that the line is the focus
• Line positive and blood negative may suggest colonization only

In cases of Staphylococcus aureus, Pseudomonas sp., or Candida sp. unless there is some tremendously good reason to keep the line it should be removed.

• Failure to remove the focus/line can be associated with adverse outcomes including metastatic infection and death.
  
• Changing over a wire or reinsertion at the same side is not ideal but sometimes the only solution.
• If the line is not medically necessary and is easy to remove without complication it should probably be removed in most line related infections.
  

Treatment is then dependent on the presence or absence of metastatic infection and should be tailored to the organism and its sensitivities.

• One should be vigilant for evidence of metastatic infection or complications.
  
• Recurrent bacteremias with the same organism are highly suggestive of an occult/endovascular focus.
  

I will also take this moment to point out that for sensitive Staphylococcus aureus treatment with VANCOMYCIN is inferior to a BETA-LACTAM in the non-severly allergic patient.

---

We also talked about two interesting pathogens involved in this case:

• Staphylococcus lugdunensis which is a coagulase-negative staphylococci which has virulence similar to Staphyloccocus aureus and is a cause of endovascular infections such as native-valve infective endocarditis
• Achromobacter xylosoxidans ss xylosoxidans which is a rare gram negative rod which has been known to cause infections such as bacteremia and more rarely pneumonia, abscesses and meningitis. Patients with malignancies seem to be particularly at risk.
  

Decision making in Community Acquired Pneumonia

Read a great article published in CID on Aug 1, 2008. SMART-COP predicts people with CAP who will require admission to intensive care requiring ventillatory or vasopressor support. It does so better than the PORT score or CURB-65 which really only predict death.

ACC cardiology guidelines

As mentioned at noon rounds today, the ACC has some excellent guidelines available for you to learn from. I have used them extensively during my residency.

The pocket guidelines are the most succinct and easy to read.

I also really like the BMJ series called the ABCs of clinical electrocardiography which really helped me improve my skill at reading ECGs.

Day #7 - Sickle Cell Anemia

Today's case was on sickle cell anemia presenting with vaso-occlusive bony crisis. The take home big picture points include:

• IV hydration and correction of hypoxemia
• Exclude or treat infection
• Appropriate analgesia (morphine, hydromorphone) using narcotic sparing treatments such as ketorolac (5 days maximum ketorolac, use with H2/PPI)
• Avoid transfusions unless symptomatic or <50-60.>
• Chest crisis, stroke, splenic crisis should be considered for exchange transfusion
  
• All patients should be on folic acid
• Consider hydroxyurea in those with >=3 episodes/year. See this article.
  

Up to Date has an excellent review of sickle cell anemia that is very comprehensive. We will also have a noon rounds session on sickle cell anemia on August 26th.

Management of DKA

Thank you to those who participated in our small group discussion on management of DKA. This was a first attempt at running such a session, so hopefully the next one will be even more effective.

The takeaway points (as I see them are):
* Stabilize the patient first while doing everything else

• large bore IVs with NS for hypovolemia
• foley as required
• think about arterial line in the sicker patients
  

* History/Px/Labs to look for volume status and precipitant
* Insulin:

• When you know the K+ isn't very low start the insulin
• 0.1u/kg bolus then rate 0.1u/hr titrated to IV sliding scale
  
• If glucose not falling can increase the dose, but be sure they are volume replete
• Add dextrose (D5W or 2/3-1/3) when glucose <~13
• Continue until patient has normal glucose and no anion gap and is ready to eat

* Potassium

• Add K+ to the IV as soon as they are urinating and K+ <5
• Oral repletion for hypokalemia in addition to IV.
  
• Hold insulin when K+ <3.3

* Sodium/Water Balance

• Use IV NS until you have reversed the signs of shock
• Then change to a hypotonic fluid like 1/2NS or 2/3-1/3 or D5W

* Treat the precipitant

As promised, here is my favorite article on the management of DKA/HONK.

This is my favorite figure from the article if you don't want to read it all:

Day #4 - Acute Monoarthritis

Today the discussant spoke about the approach to acute monoarthritis. It was a very articulate presentation and your participation was excellent.

To clarify the point on treatment:

• CEFTRIAXONE 2g IV q24h will cover most organisms including GC, most streptococci, Staph. aureus and many gram negatives. It is not the ideal agent for Staph. aureus, so if it turns out to be methicillin *sensitive* staph. aureus you should change to ANCEF (1g IV q8) or CLOXAILLIN (2g IV q6)
• Is MRSA a possibility or is this a prosthetic joint? --> ADD VANCOMYCIN (renal dose)
• Is there reason to worry about pseudomonas? --> I would suggest VANCO+CEFTAZADIME and ID consult.

• Prosthetic Joint = Call ortho. Probably should not be admitted to medicine if septic prosthetic joint is the main reason they are in hospital -- they need to go to the OR for wash-out and, in my experience, this is much less likely if they are admitted to GIM instead of orthopedics. Should get ID consult as well.

This article from JAMA is an excellent reference on making an evidence based diagnosis of septic arthritis on history, physical and laboratory examination.
VIDEO: How to do an arthrocentesis of the knee

Highlights include:

Risk Factors: Age, DM, rheumatoid arthritis, joint surgery, hip/knee prosthesis, HIV infection, skin infection, (unprotected sexual intercourse for GC)

History: Pain and swelling are present >80% of the time; fever is present only 60% rigors and chills less than that.

Synovial Fluid Exam (LR less than 0.1 rules out; LR >10 rules it in)

• WBC <=25,000 unlikely septic arthritis (LR 0.32) unless immunosuppressed
• WBC >=25,000 LR 2.9
• WBC >=50,000 LR 7.7
• WBC >100,000 LR 28

• PMNs <90%>
• PMNs >90% LR 3.4

Important to note that measurement of glucose, protein, lactate do not appear to be helpful according to the literature. Also note that LDH in the joint may have some utility in ruling out as LDH less than 250 has a good NPV; but the number included in the studies are small

Day#3 - Congestive Heart Failure

Today in morning report the team presented a case of presumed decompensated congestive heart failure. The discussant reviewed a good approach to the diagnosis and etiology of CHF. He also talked about constrictive pericarditis and quoted an article "Undercover and Overlooked"

**You can access NEJM online for free @ the UHN. At home you can access it for free if you have a U of T library card using this link.

Regarding CHF management:

In the acute setting treatment can be loosely summarized by the nmemonic LMNOP:

L = lasix --> usually IV, dose dependent on whether they are
M = morphine --> small IV doses help with the sensation of dyspnea and can also venodilate reducing preload
N = nitrates --> as the discussant pointed out, often patients are hypertensive related to sympathetic drive. Adding nitrates will reduce preload and afterload through veno/arteriodilation
O = oxygen --> this can include Non-Invasive Positive Pressure Ventillation (NIPPV) which can be helpful in acute CHF as the positive pressure can help reduce preload as well as help overcome resistance in the lung caused by fluids
P = position --> sit the patient upright, swing their legs over the side of the bed. This will decrease preload.

The ACC has a fantastic series of pocket guidelines for many cardiac conditions. I have always liked their ACC Chronic Congestive Heart Failure Guidelines.

Day # 2 - ACLS

Today at TGH talked about running a "code blue" and the ACLS algorithms for pulseless VF/VT and asystole/PEA.

The full ACLS guidelines are available online here. This is an exhaustive document. I found the cardiac arrest and tachycardia/bradycardia documents the most helpful -- although the ligtning strike article was interesting.

Contrary to what was suggested, intracardiac epinephrine is not discussed in the guidelines and there is not an intracardiac epinephrine needle on the crash cart. Nevertheless it is an interesting concept.

This link appears modestly usefull as well -- though I have not gone through to verify the content of each flowchart.

Important take home messages:
* The first pulse you take is your own
* Every code needs a leader
* Quality CPR -> Check pulse/rhythm -> Quality CPR/Drugs/Shock -> Repeat
* Look for reversible causes (5H's, 5T's)
* Ask for opinions when considering stopping
* Document well
* Debrief with your team

Day #1 - The Beginning of the Journey

Today is July 1st. It is the beginning of the academic year.

For my new intern colleagues this is the first day you will ever test out their new title, Doctor. Now it is time that you really grow into it. Your senior residents have all been there and we all remember what it was like to start out.

Know that you are fully supported if you need help or don't know exactly what to do. There is no shame in asking for help; rather it is encouraged. Nevertheless, I humbly suggest that you make up your mind before "phoning a friend". Decide what you think is going on and what your plan would be for management. Making these decisions by yourself is how you will grow. Recognize that actually implementing your plan without help is not required for the learning exercise. That is what a discussion with your senior resident or attending physician is for if you are truly unsure of what to do.

This site will chronicle this year. I hope to use it to link to teaching materials, case discussions and social events.