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 #159 - Fever of Unknown Origin - The Return

Due to fun rounds time constraints -- will point you to my previous blogs on FUO -- 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.

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.

Day #114 - Sickle Cell Anemia

Today we discussed a case of severe sickle cell anemia (previous blog). We spent a lot of time discussing the chronic end organ complications of sickle cell anemia, some of which include:

• CNS
  
  • Stroke and chronic long term sequelae
    
• Cardiac
  
  • Restrictive cardiomyopathy (hemochromotosis)
  • Pulmonary hypertension and cor pulmonale
• Respiratory
  
  • Mixed Restictive/Obstructive lung disease
• GI/Hepatic
  
  • Cirrhosis and portal hypertension (hemochromatosis)
  • Gallstones
• Renal failure
• MSK/Derm
  
  • Avascular necrosis and associated osteoarthritis
  • Bony infarcts
  • Artritis of hemochromatosis
  • Chronic skin ulcers
    
• Infections
  
  • functional asplenia and risk of encapsulated infection
  • Transfusion related -- HIV, HCV, HBV (especially pre-screening)
• Priapism
  
• 
  

• 
  

Day #113 - Fever of Unknown Origin (FUO)

Today we talked about a case of true FUO. The discussant is published on the issue and I have linked to that article in previous blogs.

FUO blog #1
FUO blog #2

Day #112 - Severe Aortic Stenosis

I hope that you enjoyed today's case. The discussant took us through an excellent classification and approach to congestive heart failure. We then unfortunately ran out of time part way through the best part -- which was the management options, including new and exciting interventional techniques for severe aortic stenosis.

Approach to Etiologies of CHF:

• Arrythmia -- either too fast or too slow
  
• Valvular -- aortic stenosis/regurgitation, mitral regurgitation/stenosis, less likely pulmonic and tricuspid stenosis/regurgitation
  
• Pericardial disease -- tamponade, constrictive pericarditis
• Myocardial disease -- toxins (like chemotherapy), infiltration/restriction (i.e amyloid), genetic (hypertrophic cardiomyopathy), idiopathic/infectious, hypertension with LVH (diastolic dysfunction)
• Ischemia -- either old ischemia and infarcts or acute ischemia
• High output -- severe anaemia, paget's disease of bone, arteriovenous malformations

Aortic Stenosis (is a SADD disease):

When symptomatic it can present with:

• S - Syncope
• A - Angina
• D - Dyspnea (CHF)
• D - Death

Survival in patients with symptomatic severe aortic stenosis is poor without valve replacement surgery

The ACC recommendations for valve replacement are summarized below:


In patients who can't have valve replacement the options include:

• Palliation
• Maximal medical therapy (symptomatic)
• Interventional - Valvuloplasty (palliative) or percutaneous valve replacement
  

I have previously blogged about congestive heart failure here and briefly discussed cardiomyopathy here.
I have previously blogged about the Jugular venous pressure and its waveforms here

Day #111 - TB Pleuritis

Today we talked about a great case.

There is a *great* free resource called the Canadian Tuberculosis Standards available here.

First we talked about the diagnosis and treatment of latent tuberculosis infection.

Diagnosis:

• Positive mantoux test
  
  • Interpret in context of patient's history
    
    • less than 5mm - negative (or false negative in immunosuppressed or very ill patient)
    • 5mm-10mm - HIV, close contact with known case, chest xray evidence of old TB as fibronodular disease, children, immunosuppression (chemo, TNF alpha, high dose steroids)
    • Greater than 10 - positive for all others
    • Increase in 6 from previous known positive.
      
  • BCG -- only consider BCG as the cause of a TST if it was given after 12 months of age to a patient from a low risk country and does not have radiographic evidence of old TB
• Can consider inferferon based assay, though this is not the standard
  
• Evidence of prior tuberculosis on imaging
• No evidence of active disease

Treatment:

• Tend to treat people who are at the highest risk of re-activating or those with the lowest risk of drug side-effects
  
  • High risk includes: HIV, organ transplant, TNF alpha inhibitors and other immunosuppression
  • Risk in health normal person is ~ 5% in first 2 years and 10% over the lifetime
  • Immigration and reactivation risk
    
• INH 300mg PO OD x 9 months with Vitamin B6 25mg po OD
• Alternative (not as good): RIFAMPIN 600mg po OD x 4 months

We then talked about diagnosis and treatment of TB pleuritis

Diagnosis:

Acute to subacute illness (2/3 present less than 1 month) with fever, pleuritic chest pain, minimally productive cough. Unilateral effusion.

• Exudative effusion
• pH usually ~ 7.4
• Glucose usually normal
  
• Lymphocytic pleocytosis (though can be neutrophils early)
  
• Usually less than 5% mesothelial cells
• AFB stain less than 10%
• Culture ~ 30% (yield may improve by inoculating into special culture media)
  
• PCR positive in 90-100% of culture positive but only 30-60% of culture negative
• Sputum positive in ~ 50%
• Pleural biopsy shows either granulomas or AFB or is culture positive in up to 95%
  

• Measurement of Adenosine Deaminase
• The future: Other novel tests

Treatment:

• INH, RIF, ETH (add PZA if sputum positive, sick, bilateral effusions, other extrapulmonary disease) x 2 months then if INF/RIF sensitive INF/RIF to complete 6 months
• Adjuvant steroids are not clearly indicated
  
• Effusion may take up to 6 months post treatment to resolve.
  

Day #110 - TTP

Diagnosis:

• Microangiopathic haemolytic anemia (>=5% fragments) with normal INR/aPTT
  
  • Classic pentad:
    
    • Fever
    • Altered mental status
    • Renal failure
    • Microangiopathic haemolytic anemia
    • Thrombocytopenia
  • Few people present with the classic pentad unless left untreated for a long time. Most present with MAHA thrombocytopenia alone.
    
  • Needs to be contrasted with Haemolytic Uremic Syndrome in children with diarrhea (E. coli 0157:H7)
  • Need to exclude DIC from sepsis or malignancy, malignant hypertension, scleroderma renal crisis, HELLP syndrome
    

Causes:

• HIV
  
• Drugs (ticlodipine, clopidogrel, quinine, valacyclovir, cyclosporin A, tacrolimus, others)
• Idiopathic/genetic
• Pregnancy associated

Management:

• Arrange transfer to specialized centre for PLEX
• In interim add steroids for idiopathic TTP
  
• In interim add FFP infusions (i.e. 1u q2h)
  

I have previously blogged about TTP here and anemia (including haemolytic anemia) and thrombocytopenia.

Day #107 - Hepatorenal Syndrome

Today we talked about acute decompensated cirrhosis with massive ascites and hepatorenal syndrome.

Hepatorenal syndrome (20% or acute renal failure in cirrhotics) (good articles here and here):

• Two types:
  
  • Type 1: Acute rise in creatinine (usually within 2 weeks)
  • Type 2: More gradual rise and usually not progressive
    
• Criteria for diagnosis (revised 2007):
  
  • Cirrhosis with ascites
    
  • Creatinine >120
  • No current or recent nephrotoxins
  • No shock
  • Doesn't improve with volume rescucitation (with albumin) and stopping diuretics x 2 days
    
  • Less then 500mg proteinuria/24h and no large hematuria or sonographic evidence of renal parenchymal disease or obstruction
• Treatment of type 1 HRS
  
  • Generally as a bridge to transplantation! Not usually on their own if transplant will never be an option
    
  • Norepinephrine infusion, or midodrine 7.5-12.5mg PO TID with octreotide 100-200mcg SC TID, or terlipressin infusion
    
    • With albumin 1g/kg on day 1 and 20-40g q24h
  • Treat 5-15 days with goal Cr <120
  • Haemodialysis should generally *not* be used as it does not improve the poor outcomes -- though can be used as a bridge to transplant
  • TIPS - in patients with CPS less than twelve and bilirubin <85 and without severe encephalopathy can have survival benefit.
    
• Outcomes
  

Alcoholic hepatitis:

• People talk about treating with corticosteroids in severe disease; however, a recent meta-analysis questions the evidence -- though perhaps the problem is we use the wrong scale to identify patients who will benefit.
• There is also evidence for pentoxyfiline, though deciding who should get this over steroids, or if they would be better in combination is still pending.
  

I have previously talked about cirrhosis and advanced cirrhosis.

Day #106 - CHF

Today our discussant took us through the case in a different way -- he spent a lot of effort attempting to teach you how senior clinicians approach cases in the middle of the night. This is a very practical approach that is different than the formal history and physical we usually discuss.

Here are some related articles to today's case:

• Multiple Myeloma (previously blogged a case of MM here)
  
• Monoclonal Gammopathy of Undetermined Significance
• Aortic Stenosis
• Lead and Renal Failure
  

Day #101 - Eosinophilia

Today we discussed a case of hypereosinophilia.

We discussed the differential diagnosis of eosinophilia including:

• Idiopathic Hypereosinophilic Syndrome (HES)
  
• Eosinophilic malignancies
• Systemic mastocytosis
  
• Associated with lymphoma (IL5 production)
  
• Infections
  
  • Parasitic (during tissue invasion): strongyloidiasis, ascariasis, hook worm, angiostronyliasis, liver flukes (fasciolysis, chlonorcis), trichenosis, filariases, paragonamiasis.
    
  • Viral: HIV
  • Fungal: Aspergillosis (especially ABPA), coccidiomycosis
    
• Allergy including asthma
  
• Medications
  
  • NSAIDS, allopurinol, phenytoid, semisynthetic penicillins, ASA
    
• Autoimmune disease
  
  • Churg-Strauss
    
• Addison's disease (usually low level)
  
• Cholesterol embolism
  

NB: from up to date: "Strongyloides can persist for decades without causing major symptoms. The infection elicits varying degrees of eosinophilia ranging from minimal to such high magnitude that it is mistaken for idiopathic hypereosinophilic syndrome."

Day #100 - Pleural Effusion/Empyema

Today we talked about the approach to pleural effusions:

1) How to do a thoracentesis

Pleural fluid can be mainly water (transudate) or exudative: blood (hemothorax), pus (empyema/complicated parapneumonic effusion), inflammatory, or chyle (chlothorax)

2) Light's Criteria for transudate vs. exudate

One of:

• Protein in pleural fluid >0.5 plasma
• LDH in pleural fluid >0.6 plasma
• LDH in pleural fluid >2/3 upper limit of normal in serum

False positive rate ~25%. Can measure SAPG (like SAAG) which if >12 suggests transudate. Do this if you had a low pre-test probablity of exudate.

This article discusses liklihood ratios for each value of these measurements and can be really helpful.

3) Management of complicated pleural effusion/empyema (great article here)

• • "The Sun Should Never Set of An Undrainded [Unsampled] Parapneumonic Effusion"
    
  • Sample the fluid at least
  • If >50% of lung has effusion, loculated, air-fluid levels, pleural thickening or pleural enhancement on CT highly suggestive that you will need drainage
  • Aspiration of frank pus, anaerobic smell, positive gram stain/culture, pH below 7.2, LDH >1000 imply you will need drainage
  • Drainage options include:
    
    • repeated thoracentesis
    • pig tail catheter (probably safer than surgical chest tube, less morbidity, but more likely to become clogged if frank pus. can also be inserted by seldinger technique with initial thoracentesis)
      
    • surgical chest tube (probably required for very thick, poorly flowing purulent material. higher morbidity than pig-tail)
      
    • VATS drainage: for failure of above, for patients with chronic empyema, ongoing sepsis, if need for decortication of "trapped lung"

Shameless self plug: here is my talk on the epidemiology of pneumococcal empyema.

Day #99 - PCP Pneumonia

Today we talked about a classic case of PCP pneumonia as a presenting illness for HIV.

Classically PCP presents with progressive dyspnea, usually initially with exertion then at rest, with dry hacking cough and fever. Classically the respiratory exam is relatively normal (sometimes there is a pleural rub) despite often remarkably abnormal chest x-ray. The classic x-ray, shown here, is of bilateral perihilar infiltrates.

LDH is usually elevated but can be normal in up to 10%. LDH can also be elvated in a number of other infections and malignancies.

Exercise induced desaturation is classic and one can do walking oximetry on their patients to see this effect.

The diagnosis is confirmed by direct calciflor stain or silver stain for organisms in the sputum, induced sputum, or BAL fluid.

There is some evidence that high resolution CT can be helpful in excluding the diagnosis and perhaps saving a bronchoscopy.

Treatment is ideally TMP/SMX (dosed 15mg/kg TMP component divided TID/QID) either IV or PO depending on status. Adjunctive steroids should be considered in patients who are hypoxemic on presentation (PaO2 <70>35), who are in severe respiratory distress, or who have poor cardiopulmonary reserve. Ironically, this Toronto study showed that steroids did not influence outcome but did reduce septra intolerance. However, a cochrane metanalysis showed a NNT of 9 to prevent one death without HAART and 23 with HAART.

The use of HAART in acute PCP remains contraversial. You shouldn't stop someone's HAART if they are on it already (unless it is clearly failing); however, initiation of new HAART is unclear. Some studies show survival benefit, others mortality.

There have been many studies looking at prognostication. Obviously more severe disease at presentation is related to more adverse outcomes. This study found that age, previous history of PCP, treatment other than TMP/SMX, CMV PCR+ in the BAL, and previous use of PCP prophylaxis when diagnosed were all highly associated with mortality.

This simple prognostic score seemed to identify survivors from those who died.

I have previously written about HIV and cryptococcal meningitis here and here. These blogs link to the HIV treatment guidelines as well as the guidelines for the management of opportunistic infections.

Day #98 - Pneumonia

Today we talked about a case of pneumonia. I previously presented a case of pneumonia in "case of the week" back in July.

We stressed the management which includes:

Stabilize the patient:

• IV fluids, pressors if required, oxygen, mechanical ventilation if required. Early goal directed therapy.

Obtain microbiological specimens:

• sputum, blood culture, legionella urinary antigen if appropriate, other special tests as appropriatge
• pathogens most likely: streptococcus pneumoniae, haemophilus influenza, moraxella catarrhalis, staphylococcus aureus (including MRSA if risk factors), legionella, mycoplasma pneumoniae, chlamydia pneumoniae

Empiric antibiotic therapy (within 4h)

• Cover the most likely pathogens
• IDSA/ATS joint guidelines (are being revised to make more use of beta-lactams -- my suggestions include these guidelines and some new evidence)
• Healthy young person: macrolide (like azithromycin 500mg po x1 then 250mg po OD x 4d), beta-lactam like amoxicillin (1g po TID)
• Older, more ill:
• respiratory fluoroquinolone (like levofloxacin -- 750mg po Q24h x 5days)
• beta-lactam (ceftriaxone 1g IV q24, amoxicillin - high dose) plus macrolide
• MRSA: vancomycin (1g IV q12, renal dosed)
• Pseudomonas or other hospital acquired: Piperacillin-Tazobactam (4.5g IV q8h infuse over 4 hours) or Meropenem (1g IV q8h infuse over 4 hours)

Decision re: admission

• Prognostic score like PORT or SMART-COP.

Decision re: sending home

• Eating, drinking, mobilizing
• Off oxygen
• Ideally afebrile
• tolerating PO antibiotics
• Reliable follow up

Day #97 - Acute lymphoblastic leukemia

Today we discussed a case of a young man with severe back pain, progressive and persistent in association with anemia. We went through the clinical reasoning and arrived at the correct diagnosis (in general) as a hematologic malignancy.

The skeletal fractures were something of a mystery; however, in children early osteoporosis and fracture can be the presenting complaint so perhaps this is why! The treatment, as for hypercalcemia of malignancy includes intravenous pamidronate.

We were surprised by the finding of acute lymphoblastic leukemia, which is classically a childhood leukemia but is being seen in higher numbers in adults. The article above is a great review of ALL and this article discusses the treatment in more detail.

---

B-cell maturation and associated malignancies

---

Tumour lysis syndrome (is seen in ALL with chemotherapy):

With rapid tumour turnover, or rapid tumour death from chemotherapy there is a predisposition towards:

• Hyperuricemia(greater than 476 or 25% increase from baseline) can cause gout and renal failure
• Hyperphosphatemia (greater than 1.45) can cause renal failure
• Hypocalcemia, potentially severe (less than 1.75)
  
• Hyperkalemia (greater than 6.0)
  
• lactic acidosis

Symptoms:

• nausea, vomitting, diarhea, anorexia
• hematuria
• heart failure, arrythmias, syncope, sudden death
  
• seizure
• cramps, tetany
  

Prevention of tumour lysis syndrome complications:

• Adequate hydration, usually with a hypotonic bicarbonate solution (i.e. 2AMPS bicarb in 1L D5W)
• Diuretics if volume overloaded
• Allopurinol or rasburicase for prevention of urate nephropathy

---

A quick word on transfusions:

• Single donor HLA matched platelets for all patients who may receive a bone marrow biopsy
• Radiated blood productes
  

Day #94 - Hemoptysis

The discussant today gave an excellent approach to hemoptysis, which has a broad differential. We highlighted the importance of distinguising hemoptysis from hematemesis and epistaxis. I wanted to discuss "massive" hemoptysis in more detail.

Severe/Massive hemoptysis can be defined as blood volume >100-600cc and may be associated with hemodynamic instability and respiratory comprimise. Massive hemoptysis makes up ~5% of all hemoptysis and has a mortality quoted as up to 80%.

There are many potential causes. The most common in case series are:

• Bronchiectasis
• Tuberculosis
• Bronchogenic carcinoma
• Pneumonia
• Aspergilloma
• "Bronchitis"
• Coagulopathy
• Other -- Includes pulmonary renal syndrome, diffuse alveolar hemmorhage

Key issues in management:

1. Protect the airway. Includes positioning the patient with bleeding lung down, intubating patient with selective bronical intubation of "good lung" if possible and blockage of the "bad lung"
   
   • In cases related to the left lung, you may, at the bedside be able to advance the ETT into the right mainstem bronchus once the patient is intubated because of the anatomy
2. Supportive measures:
   
   • IV access, fluids, pressors, blood
   • Fix coagulopathies
3. Investigate/Treat:
   
   • Fiberoptic bronchscopy to visualize. If inadequate, rigid bronchoscopy. Certain therapies can be performed with the rigid bronch
     
   • If continues to bleed, and/or source can't be found angiography, usually bronical artery to localize and embolize bleeding source
   • High res CT scan if patient stable enough to move there and diagnostic uncertainty.
     

Day #93 - Staphylococcus Aureus Bacteremia

Today we talked about a patient who presented with a febrile gastrointestinal illness who happened to have two diagnoses. First, a probable viral gastroenteritis acquired from his daycare aged son. Second, a concomitant staphylococcus aureus bacteremia.

I wanted to talk about the management of Staphylococcus Aureus Bacteremia. There is a good article here on the management of MRSA bacteremia.

• Never treat staphylococcus aureus in the blood as a contaminant. Like fungus in the blood, this always needs to be treated!
• The *minimum* treatment duration is 14 days (intravenous). This is for uncomplicated infections only.
  
  • Risk factors for complication:
    
    • Longer duration of illness
    • Community acquired infection
    • Persistent fever at 72h (OR 2)
      
    • Persistent positive blood culture at 96h (OR 5)
      
    • Hemodialysis patients
    • Indwelling lines or other prosthetic material
    • MRSA
    • No identifiable source for the bacteremia (i.e. no skin or line focus)
    • Blood cultures positive within 14 hours of drawing them
      
• You need to exclude bacterial endocarditis. Present in 10-13% of cases...
  
  • TEE is much more sensitive than TTE for making this diagnosis (103 patients with SA -- TEE dx endocarditis in 25%, TTE only found 7%). In patients for whom you are planning 14d therapy (particularly those who have risk factors for complication) you should probably not rely on a TTE to exclude IE.
• Can also cause pacemaker and AICD infections
• Vertebral osteomyelitis
• Septic arthritis
• Splenic abscess (persistant fever, LUQ pain)
  
• Septic thrombophlebitis (particularly with lines)
• Septic pulmonary emboli
  
• Brain abscess/meningitis/mycotic aneurysms
• Skin/soft tissue abscesses

---

Treatment:

• Ideal treatment for MSSA is with a beta-lactam like cloxacillin or cefazolin. These are superior head to head with vancomycin for the treatment of MSSA.
• Removable foci should be removed if feasible and practical to do so
• Duration depends on complications. IE 4-6 weeks. Osteo ~6 weeks.
  

Risk of Death

• 20 to 40%!
• Age
  
• MRSA (OR 9.3)
• Blood cultures positive less than 12 hours (OR 7)
• Complication (OR 9)
  

---

In medicine we often attempt to find one unifying diagnosis that explains all symptoms -- in satisfying what is known as Occam's Razor.

The important teaching point in a complicated case like this is that the patient may have multiple diagnoses and that we must keep an open mind. In response to Occam's Razor, Hickam's Dictum states that "[the patient] can have as many diseases as the damn well please".

Day #92 - "I don't know"

Wow. What a great case. It isn't often that I truly throw my hands up and say that "I don't know" but this was one of them.

But I hope the exercise in reasoning was useful for you. I think we demonstrated an approach that was safe, cost-effective, and broad in going through the history and physical exam.

Dr. Gold previously spoke about meningitis (bacterial) and that talk is available here.

In approaching a patient with multiple infarcts we need to consider the following differential:

• Emboli - Arising from the heart or great vessels. One possibility is subacute bacterial endocarditis, particularly given the history of night sweats. I think this patient needs blood cultures drawn with blind subculturing (endocarditis blood cultures) to look for unusual pathogens like brucella. I also think he needs a trans-esophogeal echo looking for a cardiac source including a bubble study to exclude PFO. This can also look at the aortic arch.
  
• Ischemia -- Either bad luck from uncontrolled risk factors, or genetic stroke syndrome like CADASIL, Fabry's or MELAS, or thrombophilia like antiphospholipid antibody syndrome, ATIII deficiency or hyperhomocysteinemia. I would exclude thrombophilia. As a last resort I would look into genetic testing. Night sweats don't fit with ischemia.
  
• Vasculitis (Night Sweats would fit with this too)
  
  • Primary:
    
    • Primary CNS angiitis
    • GCA/Takayatsu, polyarteritis nodosa (patient has Hep B!)
      
  • Secondary due to:
    
    • Infection:
      
      • Syphilis always needs to be considered in young patients who present with stroke like syndromes.
      • HIV can do this -- though he is suppressed.
        
      • CNS TB can cause this also (usually have CNS pleocytosis).
        
      • Fungal infections like cryptococcus can do this too.
        
    • Malignancy -- Angioinvasive lymphoma or lymphovascular lymphamatosis
      
• Other

If the echo is clean, I would consequently perform angiography (MRA possibly conventional) in this patient and look for evidence of vasculitis. I think given the night sweats and epidemiology that TB needs to be excluded prior to high dose steroids. I would repeat the lumbar puncture to ensure that it is still acellular (early TB can be acellular) and again send TB studies.

I would confirm whether or not he has had a mantoux. He should have one prior to immunosuppression anyways and should be treated for latent TB if this does not represent CNS TB.

I would probably scan his chest/abdomen/pelvis to look for evidence of malignancy, lymphoma or TB disease -- or something safer than the brain to biopsy and make a diagnosis.

Ultimately he may require a stereotactic brain biopsy to exclude TB and make a diagnosis. In a young man, with progressive infarcts and no other cause, I would discuss this with the patient.

TB is treatable, thrombophilia and emboli preventable, and lymphoma may be cured but CADASIL can not so we had better be sure!

Day #91 - Palliative Care

Today we did a special rounds on palliative care. The discussant touched upon many of the important issues of symptom control, managing drug side effects, and psychosocial management.

I wanted to provide you with some information on narcotic equivalence:

1) ORAL to IV conversion is approximately 2 to 1 (i.e. 10mg oral morphine is 5mg IV morphine)

2)

Tylenol #1 = 8mg codeine
Tylenol #2 = 16mg codeine
Tylenol #3 = 30mg codeine
Tylenol #4 = 60mg codeine

** Caveat -- some people (~1/7) won't metabolize codeine. Others will metabolize codeine much more than predicted. So I tend of avoid it **

3)

60mg codeine is equal to approximately 10mg of oral morphine.

10mg of oral morphine is approximately 2mg of oral hydromorphone
30mg of oral morphine is approximately 20mg of oral oxycodone

90mg of oral morphine (OVER 24hours) is equal to approximately a 25mcg/hr fentanyl patch (OVER 24 hours)

---

Principles of analgesia titration:

Give reasonable dose on a prn basis (i.e. morphine 10mg po q2h prn or q4h prn)

Find the 24 hour total usage and apply this (minus about 25%) as a standing dose with prns approximately 10% of the total 24h dose.
(i.e. if they used 120mg, you would give them 15mg po q4h standing and 10mg po q2h prn)

Titrate daily as required (usually not by more than 25-50%)

Day #87 - Post Influenza Sepsis

This was one of my most memorable cases I presented to the discussant today. The article he asked me to send you is here.

Teaching Points:

• Influenza presents year-round but with a predominantly seasonal distribution. It is a highly transmissible virus with droplet (and possibly airborne particle) spread. Patients present with fever, malaise, lassitude, cough, myalgias, arthralgias and headache. The illness is usually self-limiting lasting approximately 1 week.
• Patients with underlying cardiac disease, respiratory disease, diabetes, or immunosuppression are at high risk of developing severe disease. Pregnant women, in the third trimester are also at risk compared to age-matched controls.
• Vaccines have been shown to have mortality and morbidity benefit, particularly amongst high risk groups. But vaccination of healthy individuals is proposed to have indirect benefit to these high-risk groups as well.
  
• A study done here in Toronto has shown that admitted patients with influenza, particularly those who are critically ill should be treated with oseltamivir. There is a reduction in mortality.
• Other notable sequelae:
  • Primary viral pneumonia or bacterial superinfection -- Most commonly streptococcus pneumoniae or staphylococcus aureus (including community acquired MRSA). This can be severe.
    
  • Viral myocarditis (rare)
  • myositis with possible rhabdomyolysis
    
  • Guillain-Barre syndrome, Influenza meningoencephalitis, Transverse myelitis

---

In this case, the patient likely had a secondary bacterial infection with lobar pneumonia, sepsis and eventually multiorgan failure. Early recognition and treatment of sepsis is important. The principle is called "Early Goal Directed Therapy". This is a protocol of interventions designed to maximize tissue perfusion and interventions in a rational way.

Essentially this means:

• IV crystalloids to maintain central venous pressure of 8-12 (JVP 3-7cm is about that if you don't have a CVP line), normal blood pressure (MAP >=65) and mixed venous oxygen saturation of >=70%
• If still not at goal with crystalloids add vasopressors (i.e. norepinephrine)
  
• If still not at goal with this and hematocrit <30%,>
• If still not at goal with this, add positive inotrope dobutamine.
  
• Early appropriate antibiotic therapy
  
• Source control -- removal of septic focus, drainage of pus, etc --> this is often the neglected step....
  
• NB: pentastarch may be harmful and so I don't use it. The use of albumin is also contraversial -- an ongoing clinical trial hopes to solve this.
  

The protocol from Rivers et. al is below:

---

Notable people affected by the 1918 pandemic:

• • Woodrow Wilson -- allegedly had meningoencephalitis while signing the treaty of Versailles
  • Harvey Cushing -- developed Guillain-Barre post-influenza
  • William Osler -- died of empyema (post influenza superinfection)
    

Day #86 - "Demand Ischemia"

Today we talked about a great case of crescendo angina and NSTEMI occurring in the context of the physiological stress of severe anemia.

The discussant reviewed a good approach to the history of chest pain:

• Character, quality, radiation, intensity -- does this sound like typical, atypical or non-cardiac chest pain? Does this sound like another diagnosis?
  
• Associated symptoms: diaphoresis, nausea, vomiting, shortness of breath, palpitations, presyncope/syncope, orthopnea, PND
• Aggravating/alleviating factors -- rest, nitroglycerin, change in position, etc.

"Demand Ischemia" is a term that I have grown to dislike. Yes, it implies that the primary pathology is not ST elevation myocardial infarction or acute plaque rupture without ST-elevation. But it still indicates myocardial damage. And this was in a patient with known coronary artery disease.

---

This patient had a macrocytic anemia as the precipitant.

Approach to macrocytic anemia:

• Problems with red blood cell production:
  
  • B12/folate deficiency (megaloblastic anemia)
    
  • Folate antagonists (i.e. methotrexate, TMP/SMX, AZT, hyrdroxyurea)
  • Alcoholism
  • Myelodysplastic syndrome
  • Multiple myeloma
    
  • Hypothyroidism
  • Liver disease (with target cells)
  • Hyperlipidemia (abnormal membranes lead to increased MCV)
• Destruction of red blood cells (or red blood cell loss)
  
  • Reticulocytosis (including "Runner's Anemia")
    
  • Congenital RBC defects like hereditary spherocytosis
    

---

B12/folate deficiency (as a cause of anemia):

• Very unlikely if MCV less than 80
  
• Folate: Serum less than 4.5nM/L diagnostic if not anorexic or fasting, otherwise need to measure RBC folate
• B12: contraversy exists as to what is normal --
  
  • >221pmol/L unlikely deficient (high sensitivity)
    
  • 148-241pmol/L possible (borderline)
    
  • less than 148 (highly likely)
    
  • If borderline/possible and wish to confirm:
    
    • Homocysteine: Elevated in folate and B12 deficiency
      
    • Urine Methyl-Melonic Acid (MMA): Elevated in B12 deficiency
    • If both normal deficiency is ruled out, if elevated 99% specific
  • Diagnosis of pernicious anemia --> measure anti-intrinsic-factor antibodies, if present than Addison's pernicious anemia is confirmed.

A great MRI of B12 deficiency and neurologic sequelae is here.

Day 85 - "That sounds bad"

Back pain is one of the most frequent complaints in medicine. Today's case highlighted why it always needs to be taken seriously.

Back Pain:

• Mechanical: Classically worsens with movement, better with rest. Can be referred down to bilateral hips, thighs.
  
  • Patterns:
    
    • Radiculopathy (classically sciatica): pain radiates in dermatome of nerve root impingement. May be associated with neurologic symptoms (weakness or numbness) in the affected area
    • Spinal Stenosis: pain radiates to legs. Worse with activity. Predictably improves with leaning forward, rest
      
  • RED FLAGS:
    
    • Night pain
    • B-Symptoms (fever, sweats, weight loss)
    • Neurological symptoms including numbness, weakness, bladder incontinence (overflow), fecal incontinence (loss of sphincter tone)
      
    • Known history of malignancy
      
• Inflammatory: associated with morning stiffness, aggravated by rest, possibly extra-axial symptoms of connective tissue disease.
• Referred pain

The examination should include a general exam looking for signs of systemic disease. A focussed exam should look for focal bony or paraspinal tenderness, and neurological findings (including rectal tone if appropriate), and associated MSK findings.

---

In the case today the patient had progressive, severe back pain in the context of 2 months of B-symptoms. He presented with cord compression.

Differential:

• Malignancy:
  
  • Most commonly prostate, breast, lung. Then RCC, lymphoma and myeloma
  • Pain (present in 95%) is often the first symptom, usually preceeding neurologic symptoms by several weeks
  • Weakness (up to 85%) and sensory losses follow. Can also have bowel/bladder dysfunction and gait ataxia.
  • Patients should get steroids (dexamethasone 10mg IV x 1 then 16mg/day in divided doses tapered over 2 weeks), intravenous pamidronate, and either neurosurgery or radiation.
    
  • This trial showed that for metastatic disease in a single area, surgery +RT was superior to RT alone for solid tumors.
• Infection:
  
  • Spinal epidural abscess
  • Vertebral osteomyeltis including Pott's disease.
• Other:
  
  • Traumatic, vertebral compression fracture

Diagnosis is best made with MRI. If MRI is not an option, the next best test would be a CT myelogram.

Day #84 - Confusion/Diabetes

We have previously talked about acute confusion and the approach here.

We previously talked about the management of diabetic emergencies (focussing on DKA) here. I linked there to my favorite article on HONK/DKA

Am going off service tomorrow so expect longer, more detailed blogs again.

Day #77 - Malaria

Today we talked about a case of a new immigrant to Canada who presented with cyclical fever and anemia. She had emigrated from a malaria endemic country and had had plasmodium malariae.

JAMA has a great article on malaria available here.

NEJM has a great article on malaria prevention available here.

Also, see my previous approach to anemia and thrombocytopenia.

Day #80 - Diarrhea

Today we talked about a case of acute diarrhea. The discussant took us through an excellent approach to acute diarrhea. Some highlights below:

Etiology:

• Infection (great article -- also IDSA diarrhea guidelines)
  
  • Viral: rotavirus, enterovirus, norovirus, etc. (CMV in immunocomprimized)
    
  • Bacterial: shigella, yersinia, e. coli, salmonella, campylobacter, C. difficile, TB (usually chronic), atypical mycobacterial (immunocomprimised)
    
  • Protozoal/Parasitic: Giardia, amebiasis, etc.
    
• Inflammatory
  
  • UC/Crohn's
• Ischemic
  
  • Small bowel -- pain out of proportion, post prandial pain
  • Large bowel -- bloody stool, colitis
• Osmotic
  
  • Laxatives, chewing gum diarrhea (xylulose), sorbitol, sucrose, post-surgical "dumping"
    
• Endocrine
  
  • Hyperthyroidism, carcinoid syndrome, VIPoma

Day #72 - Acute Cognitive Decline

We had actually discussed this case before in early August. At that time there were no myoclonic jerks, mri abnormalities, or eeg triphasic spikes suggestive of the diagnosis (now presumed) of CJD (from nejm or here from CID).



The previous discussion points on acute confusion, aphasia, and neurosyphilis are available here.

Day #71 - TTP

Today we heard about a case of a young man with a diagnosis of TTP.

I have previously talked about anemia (including approach to haemolytic anemia) and thrombocytopenia separately.

Day #70 - Fever of Unknown Origin III

I missed the rounds -- but have discussed pyrexia of unknown origin twice before. #1 and #2. Probably not as good as the discussant, but I referenced the article they were referring to.

"Special Guest Blog" by the discussant:

• Even in the "modern era", up to 1/3 of cases may go undiagnosed -these cases carry a good prognosis.
• Infections only account for 1/4 of all diagnoses.
• In certain cases without diagnosis, the benefits of liver biopsy outweigh the risks.
• Bone marrow cultures are of low diagnostic yield. Bone marrows should be performed only when there are other indications to do so ie unexplained cytopenias.
• I recently cared for a patient with FUO whose Hodgkin's disease was diagnosed on liver biopsy alone. Patients with FUO are challenging to investigate, are rewarding by virtue of the enigmatic causes that are may be found and reinforce the importance of basic principles like the careful history and physical examination.

Day #67 - Malignant Ascites

Previously I have talked about cirrhosis, ascites, and paracentesis.

The take home point from today's case was that you should be suspicious of a malignant cause of ascites when there is massive ascites without leg edema. The overwhelming majority of patients with ascites from portal hypertension will have leg edema. In this case the cause was an adenocarcinoma seen on cytology.

TB peritoneal disease can mimic a cancer. In fact, sometimes tumour markers such as CA-125 are elevated in TB peritoneal disease mimicking ovarian cancer. The diagnosis of TB peritonitis can be difficult.

The cell count is usually in the hundreds with a lymphocytic predominance.

The SAAG is usually <11.

Adenosine deaminase may be elevated -- if you can measure it.

Obviously the cytology for malignancy will be negative; however, the ascitic fluid rarely stains positive for AFB and the cultures are often negative. AMTD has a higher yield, but it is still disappointing.

Diagnosis usually requires a peritoneal biopsy sent for AFB stain as well as MTB culture.

There is a great nejm case of TB peritonitis here.

A huge (and awesome) free textbook on tuberculosis is available online here.

Day #66 - Chemotherapy Induced Cardiomyopathy

Today we heard a case of congestive heart failure in a patient who had previously received chest radiotherapy and doxorubicin (adriamycin) as part of her chemotherapy for breast cancer. Doxorubicin has the potential to cause an irreversible cardiomyopathy, and in the absence of known cardiac disease in this patient this was likely the cause of her cardiomyopathy.

There are multiple causes of cardiomyopathy including, but not limited to:

• Ischemic - secondary to MI/ischemia
• Toxic - E.g. adriamycin, alcohol
• Restrictive - Due to deposition of sustances such as amyloid, iron (hemochromatosis), glycogen breakdown products (Gaucher's), idiopathic
  
• Infectious - Viral (coxsackie virus, HIV), Chagas disease
• Auto-immune
  
• Genetic - familial dilated cardiomyopathies, hypertrophic cardiomyopathy
• Post-partum

In an earlier blog I provided a great reference for CHF management as well as the link to the nejm article on constrictive pericarditis today's discussant mentioned.