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)

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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

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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:

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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.

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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
    

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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.

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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.

Day #65 - Endocarditis

A confession -- today's case was "recycled" for your benefit -- and so is today's blog.

I have previously blogged on endocarditis, renal failure, and hyperkalemia and direct you to those sections.

Day #64 - ACLS

Today we reviewed the crash cart and the pulseless VF/VT/asystole/PEA algorithms. Here is the promised link to the ACLS materials.

http://chiefmedicalresident.blogspot.com/2008/07/day-2-acls.html