Day #140 - Adrenal Insufficiency

Today we talked about a case of a patient with symptomatic hypotension, that was not initially fluid responsive with a known history of intrabdominal malignancy and hyponatremia with hyperkalemia. The combination of these things led to the suspicion of adrenal insufficiency.

This is a classic (now 12 year old) review of adrenal insufficiency from nejm.

I have previously blogged about adrenal insufficiency here.

Day #139 - Atrial Fibrillation

Today we talked about a case of rapid atrial fibrillation.

The ACC guidelines for atrial fibrillation are here, and the ACLS tachycardia algorithm is here.

Is the AF causing severe CHF, hypotension or angina? If so manage as unstable. Otherwise manage as stable.

Unstable:

• DC Cardioversion

Stable:

• Does the patient have pre-excitation or a grade III/IV LV?
  
  • Amiodarone 150mg IV over 10 minutes, can repeat, then give 360mg IV over 6h then 540mg IV over 18h loading. Risk of cardioversion.
• No WPW or grade III/IV LV:
  
  • IV beta blocker (like metoprolol 5mg IV over 2 mins, can repeat q 5 mins x 3)
  • IV calcium channel blocker (diltiazem 0.25mg/kg IV over 2 mins, can repeat in 10 mins with 0.35mg/kg IV)
  • Follow up with oral agent of same class
• There is evidence that IV magnesium can be effective as a rate control agent, either alone or in combination.
  
• Afib of less than 48h duration (or no thrombus on TEE) can consider cardioversion either electrical or chemical.
• Does this patient need anticoagulation?
  
  • CHADS2 score if greater than or equal to 2, yes. Otherwise anti-platelet agents.
    

Consider the cause of the AF:

• Hypertension
• Structural Heart Disease
• Hyper/hypo thyroidism
• Alcohol/Stimulants
• Ischemia
• PE
• Infection
• Other stressor

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We have previously talked about septic bursitis and septic arthritis here.

I will expand on that by saying that one of the keys in effective management is source control. The septic joint should be repeatedly tapped until there is a negative culture and the cell count is dramatically decreased. If it isn't improving -- they will need surgical management. If you can't tap the joint, they will need surgical management. This is particularly a problem with "difficult" to aspirate joints like the shoulder or hip. These patients should have orthopedic surgery to wash out the joint.

Failure to drain the joint can lead to treatment failure and joint damage.

Here is a good review of the diagnosis and management of acute septic arthritis.

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1. For the record, ciprofloxacin monotherapy is a totally inappropriate empiric choice for the treatment of community acquired cellulitis (even if the patient is penicillin allergic)
   
   • Penicillin allergy is one of the bains of my existance. I direct you to this article on trying to determine if a history of penicillin allergy is "real".

Day #138 - Massive Upper GI Bleed

Today was a great case of massive upper GI bleeding. I have previously blogged about GI bleeding here and here.

The initial approach is usually endoscopic therapy. If this isn't an option, you are left with interventional radiology (angioembolization) or emergent surgery. In this case, angioembolization localized and stopped the bleeding.

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Everything you ever wanted to know about myelodysplastic syndromes and classification of the leukemias, myelodysplastic syndromes, and myeloproliferative disorders.

Day #137 - Thrombocytopenia

Today we discussed a case of a patient who has presumed immune mediated thrombocytopenia.

We discussed the approach to thrombocytopenia and then the management of ITP.

I have previously blogged about this here (including references and discussion of management).

Note that today's patient, by virtue of his cirrhosis is at a very high risk of peri-operative death from splenectomy -- he may be a candidate for rituximab if steroids fail.

Day #134 - Thrombophilia

Fantastic case today. A young woman with recurrant thromboses including one on LMWH (in the context of thrombocytopenia) manifesting as a cardiac mass! I have previously blogged about DVT/PE here.

There are a good set of clinical guidelines for DVT/PE here.

The utility of the thrombophilia workup (or possible lack thereof) will be debated at next week's medical grand rounds. You should attend.

A couple of things I wanted to highlight:

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Thrombophilias:

• Factor V Leiden/Activated Protein C resistance
• Prothrombin mutation
• Protein C and S deficiencies
• Antithrombin III deficiency
• Elevated Factor VIII
• Antiphospholipid Antibody Syndrome
• Hyperhomocysteinemia
• Heparin Induced Thrombocytopenia

Our patient had none of these for her first ~5 embolic events -- but clearly she has some underlying thrombophilia which we probably have not discovered yet. A malignancy search has been negative.

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Use of D-Dimer in established thromboembolic disease

This can be used to assist in risk stratification. A positive D-dimer (1 month post stopping warfarin) predicts patients who have a high risk of recurrent thromboembolism (original NEJM article and meta-analysis)

A Canadian study sought to identify risk factors for recurrent DVT/PE in patients with one previous idiopathic DVT/PE and found that they could predict women at low risk who could safely stop anticoagulation. These women had 0 or 1 of the following:

• Post thrombotic signs (hyperpigmentation of limb, edema, redness)
• D-Dimer greater than 250
• BMI greater than 30
• Age greater than 65

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Heparin Induced Thrombocytopenia

This is a prothrombotic condition caused by anti-PF4 antibodies which bind to heparin-platelet complexes and activate platelets. This causes platelet consumption and activation with thrombosis (arterial or venous).

If you see a patient on heparin who develops thrombocytopenia and thrombosis you had better think about this diagnosis.
The diagnosis can be challenging; however, there is a clinical prediction rule, which in association with laboratory testing can be helpful in ruling out HIT. This is called the 4 T's.

1. Thrombocytopenia:
   • Greater than 50% drop in PLT and nadir greater than 20 = 2 points
   • 30-50% drop OR nadir 10-20 = 1 point
   • less than 30% drop OR nadir less than 10 = 0 points
2. Timing:
   
   • Drop @ 5-10 days (or less than 1 day with previous heparin within 30d) = 2 points
   • Drop after day 10, or unclear when drop, or less than 1 day with previous heparin greater than 30d ago = 1 point
   • Fall less than four days without previous exposure = 0 points
3. Thrombosis
   
   • New thrombosis = 2 points
   • Progressive or recurrant thrombosis or suspected (not proven) thrombosis = 1 point
   • None = 0 points
4. oTher cause of thrombocytopenia
   
   • None = 2 points
   • Possible = 1 point
   • Definite = 0 points

Total score:

• 0-3 low (0%)
  
• 4-5 intermediate (10%)
  
• 6-8 high (80%)

NB: our patient would score a minimum of 6 (if you assume there is a possible other cause of thrombocytopenia)

The authors suggest the following algorithm for diagnosis and management of HIT using the 4T's coupled with the widely available sensitive but non-specific anti-PF4 antibody assay to screen and the difficult to obtain serotonin release assay (SRA) to confirm.

Day #133 - Unstable Angina

Today we heard a case of a female patient presenting with typical angina (although atypically described by her on the history) which was escallating in frequency. A diagnosis of unstable angina was made and she was treated according to the guidelines.

(The unstable angina/NSTEMI pocket guideline is here)

Patients should be started on:

• antiplatelet -- i.e. ASA +/-clopidogrel
• anticoagulant -- i.e. IV heparin or LMWH. In high risk patients, consider gpIIaIIIb inhibitor
• statin
• oral beta-blocker within 24 hours for patients without contraindications
• oral calcium channel blocker if contraindication to beta-blocker
• oral ACEi within 24h for patients with heart failure or LVEF less than 40%
• oxygen if hypoxemic
• nitroglycerin 0.4mg SL spray/tablets q5 mins prn (max 3 doses) for symptoms of ischemia

When admitting a patient with UA/NSTEMI, I always find it helpful to estimate their risk of complications (i.e. death/MI) using the TIMI risk score.

Patients with probable ACS of ischemic origin should have (if appropriate) early (<72h) cardiac risk stratification. If high risk patients, they should be considered for early angiography +/- angioplasty (early invasive strategy).

She then went on to have non-invasive risk stratification, which was felt to be positive and then went on to coronary angiography. This showed triple vessel disease, for which she ultimately should consider coronary artery bypass surgery.

Physical Exam - Ascites

With great thanks to a previous CMR.

Day # 132 - Decreased Level of Consciousness

Today we talked about a patient with decreased level of consciousness. We initially discussed the differential causes. I have previously blogged about this here.

This case turned out to be a deliberate ingestion of benzodiazepines. The management of benzodiazepine overdose can be approached as follows:

1. Supportive care: protect the airway (accessory devices like nasal or oral airways, intubation if necessary), support the breathing (supplimental O2, positive pressure ventillation if required), support the circulation (IV fluids, pressors etc)
2. Consider decontamination with activated charcoal (usually not done, can cause vomitting and aspiration which would comprimise your airway and of best use within 1 hour of ingestion)
3. Consider specific antidote (flumazenil) -- but use with caution as it can precipitate withdrawl (including seizure) in patients who are chronic users and can exacerbate other toxicities (i.e. tricyclics)
   
4. Look for co-ingestions (ASA, tylenol, opiates, alcohols, tricyclics, etc..)
5. Involve your friends from psychiatry in deliberate ingestions
   

This article discusses the relationship between burden of illness and suicide in the elderly. Elderly men are one of the highest risk groups for completing suicide attempts.

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Neurological examination of the comatose patient.

Remember you can still do the following:

• Cranial nerve reflexes
  
  • Pupils
  • Corneal
    
  • Dolls-Eyes
  • Caloric ear stimulation
  • Gag reflex
• Motor
  
  • Ellicit movement with noxious stimuli
  • Evaluate tone, bulk, reflexes, babinsky
• Sensory
  
  • Ellicit response with central and peripheral noxious stimuli
    

Day #131 - Upper GI Bleed secondary to Gastric Mass

Today we talked about upper GI bleeding in a young patient. We highlighted the epidemiology of upper GI bleeds and discussed the history/physical examination pertinent to Upper GI bleeding.

There is a great article here (and an article on the value of omeprazole/PPI in acute peptic ulcer bleeding here)

I have previously blogged on upper GI bleeding here.

Remember, the most common causes of significant upper GI bleeding at our hospital are peptic ulcer disease and esophageal varices. These will account for greater than 90%. The keys on the history are to look for signs/symptoms/risk factors for portal hypertension so that you can

Remember, there is not a reliable way to predict risk from a GI bleed without endoscopy for most patients. Patients with a low risk would have all of the following:

• Age less than 60
• HR less than 100 pre-volume
• BP greater than 100 pre-volume
• No postural changes (BP drop 20mm, HR increase 20, symptoms)
  
• No CHF, heart disease or other major illness
• No renal failure, cirrhosis or metastatic cancer
• Hemoglobin greater than 100
• No coagulopathy
• Reliable follow up

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This is an interesting article on the pathology of GIST. Another review is located here.

Day #126 - Hepatitis B

Today we discussed a patient with acute hepatitis on the backgroud of hepatitis B chronic infection. I have previously discussed acute hepatitis, cirrhosis and complications thereof.

I wanted to talk about hepatitis B -- Firstly, this is a great review article and so is this.

Secondly - Serologies:

• Early in infection you have the production of Hepatitis B Surface Antigen and Hepatitis B Envelope Antigen which represents active infection
• The you develop hepatitis B core IgM then core IgG. These antibodies are not protective
• If you are going to clear your infection you will next develop anti-hepatitis B-EAg antibodies, clear your E antigen and then start to clear your S-Antigen
• You then make hepatitis B surface antibodies
• There can be a window period in between clearing the S-Ag and developing the anti-HepB surface antibody where the only way you will know if they are infected is by the core antibody.

An immunized person will only have hepatitis B surface antibody

A natural, but cleared infection will have positive HepB surface antibody and core antibody and no surface antigen

A patient with chronic active hepatitis will have core antibody and in most cases hepatitis B surface antigen. They may also have E antigen (or E antibody). They will not have surface antibody.

For chronic carriers treatment depends on a number of factors -- this table provides an excellent summary:

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Note that I link to a lot of NEJM articles. This is my preferred journal. Those of you with a U of T library account have NEJM access via e-journal search in the gerstein library website. We pay for an institutional license @ U of T which you can access at home and there is a licence here at the hospital.

Those of you who would like their own subscription (b/c above don't work) can obtain one here ($~60/year for electronic only ~ $150 for print copy too)

Day #125 - Polycythemia and Hypoxemia

Today we discussed a case of a patient with polycythemia and acute hypoxemia. The most likely diagnosis was pulmonary embolism and the discussant detailed an excellent approach to the diagnosis of PE.

I have previously blogged about DVT and PE here. The article the discussant mentioned is available here

I wanted to focus on the approach to polycythemia in more detail (review article here):

Definition: Hemoglobin greater than 165 in women (hematocrit 48%) or 185 in men (hematocrit 52%).

Relative polycythemia, related to volume contraction, needs to be differentiated from absolute polycythemia in which there is an increased red cell mass.

Primary

• Polycythemia vera
• High oxygen affinity hemoglobins
• Epo receptor activating mutations
• Other

Secondary

• Chronic hypoxemia from:
  
  • Cyanotic heart disease
  • Right to left shunts (i.e. AVMs in HHT, other)
    
  • Chronic hypoxemic lung disease
  • Obstructive sleep apnea
  • Pickwickian syndrome (obesity hypoventillation)
  • Living at altitude
  • Chronic carbon monoxide poisoning! (Including smoker's polycythemia)
    
• EPO overproduction (think highly vascular tumors):
  
  • Renal cell carcinoma
  • HCC
  • Uterine cancer
  • Hemangioblastoma
    

Uptodate has a good algorithm for the diagnosis of polycythemia (adaped below):


Treatment of PRV:

• ASA to prevent ischemic events
• Phlebotomy to hematocrit less than 45% in men and 42% in women
• Failing phlebotomy add hydroxyurea
• Add allopurinol in patients with symptomatic hyperuricemia or very high uric acid excretion (greater than 1100mg/day)
  

Day #124 - Pretibial Septic Bursitis

Today's case was of a painter, who did a lot of work on his hands and knees, presenting with acute onset knee pain. We discussed the differential diagnosis in detail and then focused on septic arthritis. I have previously blogged about this here and had linked to an excellent article that I recommend you reading.

In this case, the diagnosis was pretibial septic bursitis, which can mimic septic arthritis and is commonly seen in people who do labor on their hands and knees and is associated with minor traumas. The most common infectious aetiology is stapylococcus aureus.

Day #120 - Pleural Effusion and Anemia

Today we discussed a case of progressive dyspnea on exertion related to severe iron deficiency anemia and an exudative pleural effusion.

Please see my previous blogs on the evaluation of a pleural effusion here and here.

Day #119 - Adult Onset Still's Disease

This was a great case which the discussant enjoyed taking us through. I have previously blogged about fever of unknown origin here, here and here.

There was a previous special guest blog about FUO here.

Here are articles suggested by the discussant on rheumatologic causes of FUO, Adult Onset Still's Disease, and the use of IL-1 antagonists in the treatment of Still's.

Here is another review on Stills.

Day #118 - Probable Leptospirosis

Today we heard a case of a returning traveller who suffered complete cardiorespiratory collapse as part of a sepsis syndrome. In this syndrome the patient was hypotensive requiring inopressors, hypoxemic/hypercapnic requiring ventillation, coagulopathic with a microangiopathic hemolytic anemia (see TTP blog and previous anemia/thrombocytopenia blogs) from DIC, and in acute renal failure. In the context of this illness he suffered either myocarditis or a myocardial infarction related to hypoperfusion.

This was as sick as anyone can be and survive and it is a testiment to our critical care system that he did indeed survive.

We spent time discussing the approach to diarrhea, which was his initial presenting symptom.

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We then defined sepsis

SIRS Criteria:

• Fever or hypothermia
  
• WBC >12,000 or less than 4,000
• HR >90
• RR >20

Sepsis = 2 or more SIRS criteria of presumed infective etiology
Severe sepsis includes sepsis with end organ dysfunction or lactate >4
Septic shock includes severe sepsis with refractory hypotension requiring inopressors

We then talked about the approach to early goal directed therapy in sepsis.

In this case, I believe early appropriate antibiotic therapy would include:

• Vancomycin (in case of community associated MRSA in a young man)
• Meropenem (to cover streptococcus, gram negatives including ESBL/drug resistant)
• Doxycycline to cover leptospirosis

In general, in a critically ill patient like this, I will draw cultures and then use very broad spectrum coverage empirically with a plan to de-escallate when culture results are available

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The etiology in this case is unclear but I wonder about leptospirosis. I didn't really want to talk about leptospirosis in detail during the case presentation.... This is the case of leptospirosis in NEJM that I elluded to.

I have provided you with a copy of a talk I once gave on leptospirosis here.

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Free tidbits:

Here is an article on fever in the returning traveller
A good review of typhoid fever is here.