Day # 193 - Hyponatremia

Approach to hyponatremia, including references available here.

The study, highlighted by the discussant, on marathon induced hyponatremia is available here.

Remember -- the doctor may be the most dangerous factor in the treatment of hyponatremia. Overcorrection can lead to severe consequences.

Day #181 - Pulmonary Embolism

Today was a case of pulmonary embolism in a patient with advanced malignancy.

We didn't really talk about PE -- but the discussant talked about very relevant issues including end of life care, diagnostic reasoning and clinical decision making.

For your information, I have previously blogged about DVT/PE here and thrombophilia here.

Addendum: NEJM article from Jan 2009 on PE.

Day #161 - Autoimmune Haemolytic Anemia

The last morning report @ TGH. I move to MSH in January.

Today we heard a case of auto-immune haemolytic anemia presenting as symptomatic anemia. The patient may have had a prodromal illness.

This is a great article on AIHA. This one is good too.

In reading these something interesting became clear -- in what appears to be AIHA with a negative DAT there are a few possibilities.

• Subthreshold antibody (below the level of detection with DAT) -- this may be mitigated using a different method of DAT
  
• hereditary spherocytosis
• clostridial sepsis
  
• Two interesting ones include wilson's disease and Zieve's syndrome.

NB: AIHA with ITP (either together or sequentially) = Evan's Syndrome

Day #160 - Acute Hepatitis

I have previously blogged about acute hepatitis, and have linked to a great article on acetaminophen overdose. Please see here.

Day #158 - TIA (and Stroke)

Today we talked about a case of a patient with a presumed cardioembolic (atrial fibrillation mediated) TIA and evidence of old parieto-occipital stroke.

We discussed the use of anticoagulants such as warfarin in atrial fibrillation and the CHADS2 score. This patient was "warfarin allergic". Often this is an allergy to the dye in the tablets, and one can use dye free tablets.

In these patients you can also consider nicoumalone (Sintrom) which is another oral vitamin K antagonist that is structurally different (and twice as potent). An alternative (though I am unsure of its availability in Canada) is Anisindione.

This is a great review article on the use of oral vitamin K antagonists.

In acute stroke bridging with LMWH or UFH while waiting for a therapeutic INR is usually not indicated

Note that it probably would be indicated in patients with prosthetic valves who have had embolic strokes.

We also discussed TIAs and the ABCD2 score for prognosticating the risk of stroke in TIA.

Day #155 - Complicated anemia

Today we discussed a medically complex patient presenting with subacute anemia. We discussed an approach to anemia with reticulocytopenia. I have blogged about anemia a few times before (here and here (macrocytic anemia)).

This article discusses the issue of pure red cell aplasia in the context of synthetic EPO.

This Toronto study talks about the use of supplemental iron in dialysis patients.

Day #154 - Severe hypothyroidism (Myxedema Coma)

Today we discussed a case of severe hypothyroidism presenting with impaired cognition, bradycardia and hypothermia.

We discussed the treatment of severe hypothyroidism/myxedema coma:

• Supportive care
• IV levothyroxine 200-500mcg then 100mcg q24h until improving then oral 1.6mcg/kg
• After obtaining ACTH, cortisol levels, strongly consider stress dose steroids until concommitant adrenal insufficiency is excluded
• Look for precipitant (infection, MI, other)
• Empiric antibiotics for possible sepsis while awaiting cultures

This article discusses the polyglandular autoimmune syndromes.

Day #153 - Pneumocystis (PCP) Redux

Today we heard a case of PCP pneumonia with a classic presentation. For those of you who will end up doing medical education -- you should start saving up cases during your residency that you can use as exemplars of diagnoses, management, or approaches -- especially if they have key teaching points or interesting imaging. This will also help you for when you are suddenly called upon to provide impromptu teaching.

I have previously blogged in detail about PCP here. This blog links to a number of other blogs and articles that are also useful.

Day #152 - Iron Defieicency Anemia and Cirrhosis

Today we talked about an interesting case of a patient with cirrhosis (presumably alcohol and hepatitis C related) who presented with ascites, confusion, and anemia.

Cirrhosis (including approach to ascites and SBP) previously blogged here and here
Upper GI bleeding previously blogged here, here, and here.

Anemia previously blogged here and here (macrocytic anemia).

NB: One of the key teaching points in this case is that "iron deficiency anemia" is a not a diagnosis until you understand *why* the patient has iron deficiency. Are they not eating iron, not absorbing iron, losing iron (bleeding or losing in the urine in intravascular haemolysis)?

In people with no evidence of occult blood loss in the GI tract and no other evident losses, you should consider the diagnosis of celiac disease.

Day# 146 - Two cases

We talked about a case of stroke in a young patient. An approach to stroke in a young patient is outlined briefly here.

The case turned out to be meningovascular syphilis.

Here is an interesting article on the history of syphilis and another which talks about whether or not Shakespeare himself was infected.

The second case was that of massive liver enzyme elevation with synthetic dysfunction. I have previously blogged about hepatitis here.

Day #145 - Pyogenic Liver Abscess

Today we heard about a great case of pyogenic liver abscess. I wanted to clarify a few points of discussion.

Pathogenesis (most common in blue):

• Ascention of pathogens up biliary tree
• Ascention of pathogens through portal circulation. Often in the context of an intraabdominal nidus of infection like diverticulitis. May be in context of septic portal thrombophlebitis
• Cyptogenic
• Direct innoculation from trauma or iatrogenic
• Hematogenous spread from systemic infection
• Direct spread from gallbladder infection

Pathogens

• Gpc - strep milleri and other alpha haemolytic strep.
• Gnr - ecoli and klebsiella. Anaerobes (which often won't grow in culture)
  

• Amoebic liver abscess
• Hydadid cyst disease (echinococcus)

Treatment:

Pyogenic - use emperic coverage that will cover most pathogens above - I.e. Pip/tazo or ceftriaxone/metronidazole. Narrow spectrum to culture results not forgetting anaerobes

Drainage - either IR or surgical -- "Never let the sun set on undrained pus"

Amoebic - metronidazole 750po TID x 10 days followed by luminocidal agent

Hydadid - Specialized surgical care.

Day # 144 - Pulmonary Hypertension

Today we discussed a case of severe pulmonary hypertension presenting with shortness of breath and right heart failure.

There is a great review article on pulmonary hypertension here.

We initially discussed the physical exam findings in pulmonary hypertension:

JVP - Often elevated, may have CV waves if has tricuspid regurgitation, may have kussmaul's sign or abnormal abdominojugular reflux if RV failure

Palpation - RV lift/heave, epigastric heave, palpable second heart sound (P2), palpable RV S3 or S4, palpable thrill of TR

Auscultation - Loud second heart sound. May be widely split. Murmur of TR (LLSB radiating to epigastrium, apex or LUSB, holosystolic blowing murmur with respiratory increase (Carvallo's sign)). Right sided S3/S4

Abdominal Exam:

Ascites, pulsitile liver

Peripheral Exam:
Edema

We then discussed etiologies:

We then discussed the treatment options for pulmonary hypertension. This depends on the cause.

For group II, III, IV you need to try and treat the underlying problem (i.e. LV failure or MS/MR, chronic hypoxemia, sleep apnea)

The best evidence for treatment is in group I. But they are using these drugs for more and more conditions.

The options are:

Calcium channel blockers (don't really work)

Consider anticoagulation

• Phosphodiesterase inhibitors (like sildenafil)
• Prostaglandin infusion (like Flolan)
• Endothelin Receptor inhibitors (like Bosentan)

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.

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)