Thinking Fast on Hyperkalemia

Hi all.  This Dr. C filling in for Natalie today.  We had great discussions at Rapid Fire Morning Report today.

On the topic of heuristic thinking and biases here is the reference to the book Dr. Abrams brought up by Daniel Kahneman.  It's a fascinating read.

We also discussed bronchiectasis and the choice of antibiotic treatment in an exacerbattion. As Dr Sibbald mentioned, the British Society Guidelines recommend Amoxicillin as first line (often in high doses), with the caveat that previous cultures should guide therapy.  This is especially true for coverage of Pseudomonas. We did not delve into treatment of non tuberculous mycobacteria, but here is a BTS reference  as well as a more recent ATS guideline for further reading.

Lastly we had a great discussion on managing hyperkalemia.  Here is a link to an interesting article that highlights an important point that came up in our discussion:
- Up to 50% of patients with K>6.5 may have no ECG changes!! Often this is related to chronicity, with slower rises in potassium causing less ECG changes, however that level of hyperkalemia requires prompt treatment.

Finally take a look at the CMAJ article on treatment of hyperkalemia from 2010.

Cheers

Painless Jaundice!

This morning we discussed an interesting case of a patient with painless jaundice after receiving multiple courses of antibiotics, including septra, for a presumed cellulitis.

Here is an approach to painless jaundice (not an exhaustive list):

1) Prehepatic causes:

• Hemolysis: i.e. AIHA, G6PD with offending drug
• Impaired hepatic bilirubin conjugation: Gilbert's, Crigler Najjar

2) Intra-hepatic causes:

• Inflammatory: Primary biliary cirrhosis, primary sclerosing cholangitis
• Malignant: Cholangiocarcinoma, hepatocellular carcinoma
• Infectious: Chlonorcus senensis (Chinese liver fluke), Ascaris lumbricoides, Viral: HBV, HCV, EBV, CMV (but usually produces more hepatocellular picture rather than a cholestatic picture), alcoholic hepatitis
• Drug induced liver injury
• Other: NASH, liver infiltration (amyloid, sarcoid, lymphoma)

3) Post-hepatic causes:

• Cholelithiasis: common bile duct obstruction, Mirizzi syndrome where distended gallbladder causes obstruction of extrahepatic bile duct
• Pancreatic neoplasm
• Stricture post instrumentation

A little more on Drug Induced Liver Injury (DILI)

1) Types of DILI:

• Can mimic all patterns observed in primary liver disease
• Acute hepatocellular injury: increased ALT/ALP ratio
• Cholestatic injury: Isolated increase in ALP, with decrease in ALT/ALP ratio
• Granulomatous hepatitis
• Steatohepatitis
• Can present as acute or chronic liver injury
• Acute hepatocellulary injury and fulminant liver failure:
• Examples of drugs that cause acute fulminant hepatitis include: acetaminophen, isoniazid, sulfonamides, cotrimoxazole, ketoconazole, anticonvulsants
• Acute Cholestatic injury:
• Presents clinically with jaundice, pruritis, dark urine and pale stools
• Liver enzymes reveal elevated ALP, GGT and Bili.
• Common culprit drugs include: anabolic steroids, oral contraceptives, prochlorperazine, and antibiotics (septra and erythromycin)
• See the following articles for more information:
• NEJM article on DILI
• Case report of Septra induced prolonged cholestasis: http://www.ncbi.nlm.nih.gov/pubmed/1587437

Use of Fluoroquinolones

Today in morning report we had a quick discussion on the use of fluoroquinolones. Here are some pearls to consider prior to prescribing a fluoroquinolone:

• Sensitivity to UV: wear sun protection!
• Prolongation of QT interval: Check baseline ECG and repeat ECG while on medication if baseline QTc is prolonged
• Tendonopathy and tendon rupture: worse in elderly >60yrs, mainly Achilles tendon
• Rash: Immediate IgE mediated reactions and delayed type hypersensitivity reactions (maculopapular rash)
• Hepatic toxicity: may cause transaminitis and rarely acute liver injury
• Hypoglycemia: mainly seen with gatifloxacin
• Exacerbation of myasthenia gravis

Surviving Sepsis Campaign

The Surviving Sepsis Campaign came out with updated guidelines for the management of severe sepsis and Septic shock in 2012. Here is a summary. Please refer to this link to access the entire article: Surviving Sepsis Campaign

A. Initial Resuscitation:

• Recognize septic shock: defined as documented hypotension despite adequate fluid challenge and evidence of end organ hypoperfusion (lactate >4g, AKI, change in LOC, cardiac ischemia)
• Goals for the first 6 hrs:
• CVP 8-12mmHg
• MAP 65mmHg or greater
• Urine output goal 0.5mL/kg/hr
• Central venous saturation 70% or mixed venous O2 sat of 65%
• Target resuscitation to the normalization of lactate

B. Diagnosis:

• Septic w/u: cultures should be drawn prior to antibiotic administration anaerobic/aerobic at least one peripherally and one from all central lines
• If fungal infection/candidiases is suspected: use 1,3 beta-D-glucan assay, mannan and anti-mannan antibody assays
• Imagine as needed to investigate source

C. Empiric Therapy

• Administer IV abx within first hour of recogntition of shock.
• Think about potential bugs and penetration of IV abx
• Combination therapy for severe sepsis/neutropenic patients is recommended for up to 3-5 days but should be narrowed thereafter. Consider combo therapy for pseudomonas, acinetobacter and other multi-drug resistant organisms (i.e. an extended spectrum beta lactamase and gentamycin or flouroquinolone)

D. Get Source Control

• Every effort should be made to get source control within 12 hrs of identification, this may involve getting the surgeons or interventional radiology involved. Abx treatment should be limitted to 7-10 days, unless there was slow response to abx
• For example, infected peripancreatic abscess or infected necrotizing pancreatitis should be drained percutaneously or surgically once viable and non-viable tissue is demarcated.
• If percutaneous devices are a possible source infection, they should be removed promptly!

E. Infection Prevention:

• Selective oral and or digestive decontamination should be used i.e. oral chlorhexidine

Wolfram's Syndrome and secondary causes of diabetes

Today we had an interesting discussion of a patient with Wolfram's Syndrome or DIDMOAD, this generated an interesting discussion on secondary causes of insulin resistance:

1) What the heck is DIDMOAD?

• Wolfram syndrome has three genetic forms one of them being DIDMOAD
• It is an autosomal recessive disorder with incomplete penetrance, affecting 1/770 000
• DI - Diabetes insipidis: due to loss of vasopressin secreting cells, anterior pituitary dysfunction has also been described
• DM - Diabetes Mellitus: Patient typically develop diabetes in childhood requiring insulin (due to an inability to convert pro-insulin to insulin)
• OA - Optic atrophy occurs early in childhood 
• D - Deafness: sensorineural deafness

2) What are other causes of insulin resistance?

• Primary pancreatic: Infiltrative (hemochromatosis, amyloidosis), cystic fibrosis, pancreatic cancer, chronic pancreatitis, surgical removal/trauma
• Endocrine: Cushings (secondary to elevated cortisol), acromegaly, pheochromocytoma (secondary to adrenergic stimulation), Conn's (secondary to hypokalemia)
• Drugs: Steroids (increases gluconeogenesis and decreases peripheral glucose transporter), thiazide diuretics, atypical anti-psychotics, nicotinic acid, HAART therapy, ocreotide infusion, inotropes
• Unusual causes: muscular dystrophy, friedrich's ataxia, Wolfram's syndrome etc.

3) Work up and Management of hyperglycemia:

• Confirm: Repeat the accucheck
• Look for causes: 
• Known diabetes? HHS/DKA (look for precipitating factors: infarction, infection, insulin non-compliance, new diagnosis of diabetes) 
• Secondary causes of insulin resistance: i.e. medications
• Look for perpetuating factors:
• Severe hypovolemia results in both hemoconcentration and decreased GFR leading to decreased filtration of glucose
• Increased adrenergic/stress state drives gluconeogensis and insulin resistence
• Investigations:
• Physical exam to look for precipitating factors and degree of volume depletion
• Laboratory work to look for DKA/HHS and precipitating factors:
• ABG, anion gap, serum ketones, serum osmolarity, electrolytes (esp. K+), creatinine
• Septic w/u, ecg, troponin/ck, amylase/lipase
• Treatment:
• Fluids for the hyperglycemia
• IV Insulin to close the anion gap and decrease fat metabolism and the generation of ketones. Continue until the anion gap is closed
• potassium replacement
• Treat the underlying cause
• Transition to SC insulin once patient's B.G. is stable and insulin requirements have been minimal and stable and patient is eating... and in the daytime! Ensure at least 1-2 hrs of overlap.
• Please see the following article for treatment of Diabetic ketoacidosis: CMAJ 2003 Treatment of DKA/HHS

Asthma

Today we had an interesting discussion on Asthma and it's potential mimicers, here is a synopsis:

• Diagnosis:
• FEV1/FVC less than0.75-0.8 with 12%+ improvement with beta-agonist
• More than 20% variation in peak expiratory flow (PEF)
• Methacholine challenge: PC20 (Concentration required for a drop in FEV1 of 20%) less than 4mg/ml
• Measures of poor control:
• Daytime symptoms more than 4/wk and night time symptoms more than 1/wk
• Missing days of work/school
• Decreased physical activity
• Frequent exacerbations
• FEV1 or PEF less than 90% of personal best
• Need for fast-acting beta2 agonist more than 4 doses/wk
• Sputum eosinophils more than 2-3%
• Treatment of Asthma exacerbation:
• Markers of severe disease/impending respiratory collapse:
• Work of breathing: use of accessory muscles
• Hypoxia (asthma is really a problem with ventilation, when oxygenation starts to decrease that's a worrisome sign)
• Pulsus paradoxus greater than10mmHg
• Silent chest!
• Inhaled beta agonists: short acting beta 2-agonists (salbutamol, albuterol) and short acting anti-cholinergics (iptratropium) MDI with aerochamber
• Prednisone: 40-60mg Prednisone daily or if unable to take PO consider IV solumedrol for 10-14 days.
• Adjuncts: MgSO4 2mg IV, Leukotriene receptor antagonists
• Intubation if needed
• Abx if evidence of pneumonia 
• Complications of asthma that may present as worsening/non-responding asthma:
• Churg-Strauss: Medium-small vessel vasculitis that presents with worsening asthma, eosinophilia and ANCA positive in 40-60%. Other signs of vasculitis include: leukocytoclastic vasculitis (palpable purpura), mononeuritis mulitplex and less commonly RPGN.
• ABPA: Allergic bronchopulmonary aspergillosis. Major diagnostic criteria:
• Hx of asthma
• New pulmonary infiltrate
• Immediate skin sensitivity to aspergillus precipitins
• Precipitating serum antibodies to A. fumigatus
• Peripheral eosinophilia (500/mm3)
• IgE (1000ng/ml)
• Increased serum antibodies IgG, IgA, IgE
• Central bronchiectasis
• Cryptogenic Organizing pneumonia (previously called BOOP):
• A non-specific pulmonary inflammatory process manifesting as inflammation of the distal bronchioles, alveolar ducts/walls. Characterized by fever, malaise, chronic cough, areas of infiltration in CXR
• Terminology: Organizing pneumonia of determined cause and if it is "idiopathic" it is referred to as organizing pneumonia of undetermined cause or COP
• Causes of organizing pneumonia: infections (including: mycoplasma, PJP, HIV, cryptococcus), drugs (amiodarone, cocaine, bleomycine), malignancy.
• Can also occur in the context of CTD: SLE, sjogren's, dermatomyositis, etc.
• Mimicers of Asthma:
• Paradoxical vocal cord motion: the vocal cords move in during inspiration. Can be triggered by stress, exercise, airway manipulation, irritant inhalations. Presents with upper airway stridor, throat tightness, hoarseness cough. Treat with reassurance and asking the patient to "pant"
• Laryngospasm: Can be induced by URTI, presents with aphonia and choking sensation. Use of continuous positive airway pressure and heliox may help.
• "Cardiogenc wheeze": Don't miss the patient who presents with wheeze secondary to pulmonary edema (cardiogenic or non-cardiogenic)!

C. Difficile Colitis

1) Risk factors:

• Age >65yrs
• Recent antibiotic use (all and any abx use will put patients at risk for C. diff but increased risk if multiple abx and prolonged use)
• Recent hospitalization or residence in a nursing home/health care facility
• Treatment with PPI
• Comorbidities (DM, liver disease, CKD, cancer on treatment, solid organ transplant)

2) C. Diff treatment from the IDSA guidelines:

• Initial episode, mild/moderate
• WBC less than 15, Creat less than 1.5 x baseline
• Treat with metronidazole 500mg PO TID x 10-14 days
• Initial episode, severe 
• WBC greater than 15, Creat greater than 1.5 x baseline
• Treat with Vancomycin 125mg PO QID x 10-14 days
• Initial episode, severe + complicated
• WBC greater than 15, Creatinine greater than 1.5 x baseline
• PLUS toxic megacolon, ileus, shock
• Vanco 500mg PO QID and consider rectal instillation if ileus
• IV Metronidazole 500mg Q8H
• Surgical consult
• Initial recurrence
• Classify as mild/moderate/severe/complicated and treat appropriately
• Ok to treat with metronidazole if mild disease, however avoid prolonged metronidazole to avoid neurotoxicity
• Second recurrence
• Treat according to severity, otherwise treat with Vancomycin 125mg PO QID with a tapered regimen
• See the IDSA guidelines for more details: IDSA Clinical Treatment guidelines for C. diff 2010

2) Diagnosis of Toxic Megacolon:

• Etiology: IBD, infectious (c. diff, CMV, shigella, salmonella, e.coli, etamoeba histiolytica etc.)
• Diagnosis: 
• Radiographic findings (greater than 10cm) 
• At least three of: fever, elevated WBC, tachycardia, anemia, dehydration, altered sensorium, electrolyte abN, hypotension.
• Treatment: 
• Surgical consult!
• Medical Mx: ICU admission, NG tube for decompression, restart eteral feeding as soon as symptoms improve, consider IV steroids in IBD associated toxic megacolon

See this link for further information: Clostridium dificille infection Mayo Clinic Proceedings 2012

Hypercalcemia

Hypercalcemia:

Causes of hypercalcemia:
1) PTH mediated: 

• Primary- sporadic
• Secondary - Chronic renal failure
• Teritary - post renal transplant - autonomous production from hypertrophied parathyroid glands

2) Non-PTH mediated

• Malignancy mediated:

1. PTH rP - SCC (lung, H+N), solid tumours (renal, breast, bladder, ovarian)
2. Lymphoma - from activation of extra-renal 1-alpha OH and production of calcitriol
3. Bony mets: Osteoblastic (prostate, carcinoid, SCLC, hodgkins), osteolytic (myeloma, RCC, nonSCLC, NHL, melanoma)

• Non-malignancy related

1. Granulomas: Sarcoid, TB (activation of extra-renal 1-alpha OH and production of calcitriol)
2. Paget's disease: Regional areas of accelerated rate of bone remodelling resulting in abnormal bone architecture, bony pain, fractures and hypercalcemia.
3. Immobilization (often concomitant with another cause of hypercalcemia)
4. Medications: Thiazide, lithium
5. Endocrine: Hyperthyroidism, adrenal insufficiency
6. Milk alkali

Symptoms:

• Moans: Abdominal pain/constipation, nausea, anorexia
• Bones: Bony pain
• Groans: Calcium kidney stones (CaPhos or Caoxalate)
• Psychic overtones: Change in LOC, delirium

Treatment:

• The cornerstone of treatment is: FLUIDS, FLUIDS, FLUIDS. Patients are often quite hypovolemic secondary to their inability to concentrate urine and nephrogenic diabetes insipidus. The kidneys should be able to excrete the majority of excess calcium  
• Calcitonin:  4u/kg IM/SC rapid reduction in serum Ca by 1-2mmol/L. Works in 4-6 hrs.  
• Bisphosphonates:  Pamidronate 30mg, 60mg, 90mg IV. More sustained reduction in Ca, takes 1-2 days to start working.  
• Lasix:  Caution as this can cause worsening hypercalcemia from hypovolemia. Only used of pt is showing signs of volume overload from fluid resuscitation. see article from Annals of Internal Medicine: Furosemide from Hypercalcemia: An unproven yet common practice

Thanks to our palliative care physicians, we had a great palliative care MR on pain control at the end of life:
1) Opioid Equivalence:

• Codeine: 100mg PO
• Morphine: 10mg PO (5mg IV/SC)
• Oxycodone: 5mg PO
• Hydromorphone: 2mg (1mg IV/SC)

2) Opioid Side Effects:

• N/V: may resolve after a period of time
• Constipation: does not resolve over time
• Somnolence/drowsiness
• pruritis
• urinary retention

3) Opioid Toxicity:

• Myoclonus is an early sign of toxicity
• Nausea/vomitting
• myosis
• Somnolence
• Respiratory depression

4) Treatment of opioid toxicity:

• Dose reduction 25-50%
• Change type of opioid

5) Incomplete Cross Tolerance:

• Results in increased response to an equivalent dose of a different type of opioid
• Therefore, when changing to a different opioid dose should be reduced by 25-50%

Post Call Morning Report

This morning we had an interesting discussion on all patients admitted to GIM over night. Here are some interesting topics that were discussed:

1) Treatment arrhythmias associated with cocaine-associated catecholamine excess

• We discussed a complicated case of an agitated patient with recent cocaine ingestion and atrial fibrillation and signs of heart failure.
• All types of arrhythmias have been described in cocaine toxicity from wide complex-tachycardia to supraventricular tachycardia
• Arrhythmias associated with catecholamine excess include SVT, Sinus Tachy, Afib
• Supportive therapy is the mainstay: cooling, IV fluid rehydration and benzodiazepines
• Other therapies for SVT/Afib may include IV CCBs 
• For treatment of HTN may use IV phentolamine/nitroglycerine for HTN (beware of reflex tachycardia)
• It is important to avoid beta blockers in pts with possible cocaine intoxication as this results in un-opposed alpha and worsening hypertension and coronary vasoconstriction
• See the following article for more information: Cocaine toxicity and arrhythmias

2) Causes of elevated Lactate

• Type A lactic acidosis: From marked tissue hypoperfusion: Cardiogenic, septic shock, local decreased perfusion (compartment syndrome, necrotizing fasciitis), ischemic bowel, seizures (from increased O2 use)
• Type B lactic acidosis: Features of hypoperfusion are not apparent. Causes include toxin-induced impairment of cellular metabolism. causes include: liver failure (from impaired lactic acid utilization in gluconeogenesis in the liver), metformin use in renal failure (theoretical), malignancy (from direct production by malignant cells), cyanide, alcoholism, diabetes.

3) Causes of low BP not responding to fluids

• In the absence of cardiogenic or septic shock think of more unusual causes of low BP:
• Anaphylaxis
• Adrenal insufficiency - mets to adrenals, infarction of adrenals secondary to severe infection (Waterhouse-Friederichsen), hemorrhage/adrenal vein thrombosis, 
• Hidden bleeding: retroperitoneal

Palliative Care Resources

Palliative Care Articles:

This week is palliative care week. Check out the following resources for further reading (Courtesy of Dr. Goche):

• Withholding Nutrition at the End of Life - Cleveland Clinic
• This is a great article on the ethics and legality of withholding nutrition at the end of life and the evidence behind why it may be beneficial at the end of life to withhold nutrition.
• Delirium in Advanced Cancer Patients - Palliative Medicine 2004
• This article discusses the precipitants, preventative approaches and treatment options for delirium in advanced cancer patients.
• Do Opioids Precipitate Death? Canadian Family Physician 2010
• This is a thought provoking article on how to kill symptoms without killing the patient.
• Discussing Do Not Resuscitate - Journal of Clinical Oncology 2001
• This article is an excellent article on how to approach a DNR discussion
• A request for non-disclosure: Don't tell mother
• This is an excellent article discussing the ethical dilemma's around non-disclosure, when families ask that their loved one not be told that they have a terminal illness. This article talks about how to approach these situations practically as physicians.

Hypertensive Emergency

Today we discussed a patient with a hypertensive emergency. Here are some key points:
1) Classification of HTN:

• HTNsive urgency: SBP>180 or DBP>120 without end-organ damage 
• HTNsive emergency: Acute severe hypertension with end organ damage
• Malignant HTN: Hypertension with papilledema, renal involvement or microangiopathic hemolytic anemia.

2) End organ damage in HTN (head to toe)

• CNS: Encephalopathy (confusion), seizures, intracranial hemorrhage, SAH, and lacunar infarcts. Radiographic finding called PRES (posterior reversible encephalopathy syndrome) characterized by posterior symmetric white matter edema seen on CT
• Optic: retinal hemorrhages, exudates, papilledema and vision loss
• Cardiac: acute MI, aortic dissection, acute heart failure with pulmonary edema
• Renal: AKI, hypertensive nephrosclerosis (over time)
• Hematologic: microangiopathic hemolytic anemia

3) HTNsive retinopathy:

• Mild — Retinal arteriolar narrowing related to vasospasm, arteriolar wall thickening or opacification, and arteriovenous nicking, referred to as nipping
• Moderate — Hemorrhages, either flame or dot-shaped, cotton-wool spots, hard exudates, and microaneurysms
• Severe — Some or all of the above, plus optic disc edema. The presence of papilledema mandates rapid lowering of the blood pressure.

4) Secondary causes of HTN: 

• Endocrine: Cushing's syndrome, pheochromocytoma, aldosterone producing tumour (Conn's syndrome), acromegaly, hyper/hypothyroidism (these do not typically present as emergency/urgency)
• Anatomic: Coarctation of the aorta
• Renal: Renal artery stenosis (atherosclerosis, fibromuscular dysplasia), renal parenchymal disease, polycystic kidney disease
• Drugs: Cocaine, MAOI and tyramine containing foods, rapid withdrawal of clonidine/propanolol
• Pregnancy: Pre-eclampsia and HELLP syndrome

5) Treatment goals:

• Hypertensive emergency: Lower the BP by 25% of the MAP in the first 24 hrs or until symptoms resolve (i.e. patient stops seizing)
• Hypertensive urgency: Safer to lower the BP over days to weeks

6) Practical treatment and specific situations:

• If HTN emergency consider admission to ICU for arterial line and monitored lowering of BP
• Labetalol 10mg IV bolus followed by infusion (can repeat bolus if necessary)
• Nitroprosuside 0.25-0.5mcg/kg/min (beware of cyanide toxicity if prolonged treatment >48hrs)
• Hydralazine (can cause reflex tachycardia, so better if pt beta blocked prior to starting)
• Catecholamine driven HTN (Cocaine, MAOI, Pheo): use an alpha blocker (phentolamine 5-10mg IV Q5-15 min). Beware of giving beta-blockers as this can result in unopposed alpha and worsening HTN
• Pre-eclampsia: labetalol IV and MgSO4
• Alcohol withdrawal: Benzodiazepines
• Aortic dissection: Avoid using vasodilators initially (i.e. nitroprusside) as this can cause a reflex tachycardia and sheer stress on the aorta. Start with beta blocker and add nitroprusside if BP still not well controlled.

Today Dr. Okrainec led us through an interesting case of an unstable patient. The following are some Clinical Pearls about the management of an acutely ill patient:

1) CAB's & MOIF +/- DONT

• Circulation: start by assessing the patient's circulation (pulse, BP and HR), feel the extremities to assess for perfusion (cold vs warm). A cool mottled patient is a sign of peripheral vasoconstriction which occurs with hypovolemia or cardiogenic shock. Warm extremities indicate a distributive picture (sepsis or anaphylaxis). If BP low, consider bolusing IV fluids using a pressurized bag, crystalloids have been shown to be equivalent to colloids.
• Airway/Breathing: Signs of resp distress: tri-poding, paradoxical abdominal breathing (Belly in with inspiration, out with expiration), quiet chest are all indicative of impending resp failure. Also assess GCS for ability to protect the airway. 
• MOIF: Monitor, Oxygen, IV x 2 and Foley. It is important to ensure the patient is being monitored (i.e. cardiac monitor or nurse at bedside to do frequent vitals). The foley catheter is useful for assessing renal perfusion

2) Primary Survey

• Once you have assessed the CAB's and initiated initial management (i.e. IV fluids, CPR and ACLS protocol if pulseless) you can do a primary survey
• The primary survey consists of a quick physical assessment to rule out/in causes of shock:
• GCS: Pupils (look for a toxidrome), focal neuro deficits, meningismus
• CVS: JVP (signs of tamponade, HF, PE), new murmurs (acute valvular rupture, aortic dissection)
• Resp: equal air entry? (signs of pneumothorax)
• Abdo: signs of perforated viscus, intra-abdo or retroperitoneal bleed (ecchymosis), check the diaper for melena/blood
• Extrem: signs of DVT
• Assess around the patient: PCA pump (opiod toxicity)? Heparin drip (bleeding risk)?

3) Initial management:

• DONT: the universal antitodes for decreased LOC (Dextrose, Oxygen, Naloxone, Thiamine)
• IV fluids: wide open and on a pressure bag (or use a BP cuff)
• STAT labs: ABG, CBC, lytes, creat, INR/PTT, lactate, blood C&S, liver enzymes, glucose, troponin/CK. The ABG can tell you roughly the lytes and hgb. Don't forget to look at pt's recent labs
• STAT investigations based on presentation: ECG, portable CXR, bedside ECHO
• Low BP resistant to IV fluids: consider giving empiric Abx (early goal directed therapy), consider stress dose of steroids if risk of adrenal insufficiency
• Low BP resistant to IV fluids: consider giving peripheral inotropic support (phenylephrine 100-200mcg IV bolus, dopamine 10-20mcg/kg/min) can give through peripheral IV for a short period
• Signs of bleeding: give blood.

4) Definitive management:

• Call ICU and arrange for transfer once CAB's are relatively stable

Today we spoke about some interesting cases that were admitted over night, here is a synopsis of the different cases we discussed:

1) Does this patient have septic arthritis?

• Identifiable risk factors and arthrocentesis are most useful for predicting septic arthritis. Physical examination and clinical history are less helpful due to non-specific symptoms and signs. 
• Age 80+y (LR 3.5)
• Hx rheumatoid arthritis (LR 2.5)
• Hx DMII (LR 2.7)
• Recent join Sx (LR 6.9)
• Prosthetic hip/knee (LR 3.1)
• Overlying skin infection and prosthetic joint (LR 15)
• WBC in synovial fluid: >25, 000 (LR 2.9), >50, 000 (LR7.7), >100,000 (LR28)
• Percentage PMN in synovial fluid >90% (LR 3.4)
• Not helpful: presence/absence of fever, ESR/CRP, peripheral WBC
• Imaging
• Ultrasound can be used to identify an effusion
• MRI best for looking for: fractures not seen on radiograph, signs of osteomyelitis, early signs of AVN and for effusions.
• Management issues:
• Joint destruction can occur within 48 hrs of septic arthritis. Therefore, should get orthopedics involved early as drainage of purulent synovial fluid is important to prevent joint destruction.

Does this patient have septic arthritis - JAMA

2) What is minute ventilation?

• Tidal volume: Quantity of air moved into and out of lungs during a normal breath (normal is 500cc)
• Minute ventilation: Quantity of air moved into and out of lungs during 1 minute (normal is 5-6L)
• Therefore, the maximal L/min of O2 that can be delivered by NP is 6L/min, beyond that, you are not giving any more O2 to the patient, this is approximately equal to FiO2 of 40%
• Delivery of oxygen is limitted by the entrainment of ambient room air (FiO2 of 21%). To increase the amount of O2 delivered you must control to amount of entrained air
• Non-rebreather masks draw oxygen from a reservoir with a one way valve that directs exhaled air out of the mask, thereby limiting the amount of entrained air. These can deliver up to 100% FiO2.

3) Pulmonary Aspergillosis

• Aspergillus is a fungus that is basically ubiquitous, found in both outdoor and indoor environments
• There are 4 classic presentations:
• Allergic bronchopulmonary aspergillosis (ABPA) - common in ashtmatics and CF patients
• Chronic necrotizing pulmonary aspergillosis (CNPA) - common in immunocompromised patients or patients with underlying lung disease
• Aspergilloma: a fungus ball that can grow in pre-existing cavities ie. from previous TB, emphysema, PCP
• Invasive pulmonary aspergillosis (IPA) - occurs in severely immunocompromised hosts with neutropenia or post HSCT

Invasive Pulmonary Aspergillosis

• Diagnosis:
• Aspergillus can be a colonizer, so diagnosis is not made solely on the basis of sputum cultures
• The diagnosis of IPA is based on histopathologic evidence of aspergillus invading lung tissue
• Diagnostic criteria for ABPA:
• Hx of asthma, immediate skin sensitivity to aspergillus Ag, aspergillus precipitins, Elevated specific IgG, E, A to aspergillus, central bronchiectasis, serum IgE >1000ng/ml, elevated eosinophils >500/mm, lung infiltrates on CXR
• Treatment
• For IPA, tx should be initiated as soon as there is a clinical suspicion and while confirmatory testing is done.
• Tx depends on the degree of infection. For IPA/CNPA, voriconazole/itraconazole is first line, can use IV liposomal amphotericin b or IV voriconazole for severe infections
• First line treatment of ABPA is corticosteroids, can use itra or vori as steroid sparing agent

Review of Pulmonary aspergillosis

Pituitary Macroadenoma

Approach to Pituitary Macroadenoma

• Pituitary adenomas are classified based on size and function:
• Macroadenoma vs Microadenoma
• Functioning vs non-functioning
• Causes problems by:
• Hypersecretion: Most common are gonadotroph secreting adenomas, but they are hardest to recognize as they secrete inefficiently and the effects are not easily noticed; prolactin (PRL), responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone (GH), responsible for acromegaly; adrenocorticotropic hormone (ACTH), responsible for Cushing's disease; thyroid-stinulating hormone (TSH), responsible for hyperthyroidism. 
• Depressed secretion of hormones: Hypopituitarism, in the order of: GH, LH/FSH, TSH, ACTH, PRL (aka Go Look For The Adenoma Please)
• Mechanical compression
• Expansion of dura causes headaches
• Superior invasion: affects optic chiasm and causes bitemporal hemianopsia
• Inferior invasion: Through cribriform plate into sphenoid sinus causing CSF rhinorrea and risk of meningitis
• Lateral invasion: Cavernous sinus/internal carotid artery and cranial nerves 3, 4, 6, 5 (V1/V2)

• Investigation:
• Mechanical compression/extension: 
• Assessed by MRI
• Also can do visual field testing
• Hormone secretion:
• GH: is normally secreted in a diurnal pattern and is suppressed by glucose load. Tested by doing an oral glucose tolerance test. Also can test IGF-1 which does not change hour by hour and reflects integrated GH secretion during the previous 24hrs. Also can test response to OGTT, as patients have insulin resistance.
• TSH/T3/T4
• Cortisol: Screening tests: 24 UFC, late night salivary cortisol, 1mg Dex suppression test
• Prolactin: Prolactin level
• Hormone suppression:
• GH, LH/FSH/Testosterone, TSH, AM cortisol, prolactin
• Comorbidities:
• If patient found to have GH secreting adenoma should look for visceral organ effects:
• Colonoscopy to look for polyps/colon ca
• ECHO to look for cardiomyopathy
• BP to look for HTN
• Fasting BG, OGTT to screen for diabetes
• Screen for obstructive sleep apnea

• Management:
• Surgical indications:
• A visual field deficit due to the lesion or other visual abN
• Adenoma abutting the optic chiasm on MRI
• Pituitary apoplexy with visual disturbance
• Hypersecreting tumour other than prolactinoma
• Specific situations
• GH secreting adenoma: First line is surgery. Medical therapies include somatostatin analogues (octreotide/lanreotide) and dopamine agonist (cabergoline) and GH receptor antagonists (Pegvisomant). Can also use radiation (fractionated or by Gamma knife).
• ACTH secreting tumour: primary therapy is surgery
• Prolactinoma: Can use medical therapy with DA agonist.
• Micro-incidentalomas
• Follow-up MRI in 1 yr and then Q1-2 y thereafter
• If grows significantly (in proportion to original size) then consider surgery
• Macro-incidentalomas
• Follow up MRI in 6 months then Q1yr
• Evaluate for hypopituitarism and evaluate the visual fields
• If there is tumour growth, VF abN or hypopit consider surgery

See the Endocrine Society Practice Guidelines for an Approach to Pituitary Incidentaloma

Fever in a Returning Traveler

Approach to fever in the returning traveler:

1) History:

• Detailed travel hx with dates (to calculate incubation period)
• Exposure history (mosquito bites, water, food)
• Visiting friends and relatives vs staying in tourist areas
• associated signs and symptoms
• Duration and pattern of fever
• immunizations tatus
• Use and adherence to antimalarial chemoprophylaxis

2) Differential Diagnosis (not an exhaustive list!)

• Must rule out MALARIA
• Incubation period: anywhere from 2 wks to a year.
• Plasmodium falciparum: must be immediately ruled out as can be rapidly fatal
• Non-falciparum (P. vivax, P. ovale, P. malariae, P. knowlesi) cause febrile illness but are rarely fatal
• Must keep malaria on the differential, even if on chemoprophylaxis due to resistance
• "hectic" fever +/- headache, cough, GI problems.
• Invx: thick and thin smears x 3, rapid antigen testing, CBC (thrombocytopenia without leukocytosis is characteristic, may have anemia from hemolysis), bili, liver enzymes
• Complications: altered LOC, seizures, acidosis, ARDS, liver failure, severe hemolysis, renal failure, cerebral malaria
• Must start antimalarials parenterally if severe infection or if levels exceed 4% of visible erthrocytes
• Dengue
•  Caused by a mosquito-borne flavivirus in tropical and subtropical areas
• Incubation period of 4-7 days
• Clinical Sx: lymphadenopathy, erythema/nonspecific maculpapular rash, leukopenia and thrombocytopenia
• Serious infection: dengue shock and dengue hemorrhagic fever
• Clinical diagnosis + confirmed with serum antibody titers
• Rickettsia
• Triad of fever + headache + myalgia
• Examples: African tick typhus, Mediterranean tick typhus, scrub typhus
• Transmitted by arthropods (painless eschar at inoculation site) in grassy areas
• Leptospirosis
• History of exposure to fresh water
• fever+ myalgia + headache + rash (Conjunctival suffusion is a diagnostic sign)
• Typhoid
•  Causal agent: Salmonella enterica. Fecal oral transmission
• Sx of fever+abdo distension + constipation+lymphadenopathy
• Invx: Leukopenia +thrombocytopneia. Dx by blood C+S.
• Treated with fluoroquinolone/3rd gen cephalosporin

See the following article for further details: Illness after international Travel 

Thyrotoxicosis

Today we talked about an interesting patient with thyrotoxicosis, here are some things we discussed

1) Thyrotoxicosis vs Hyperthyroidism

• Thyrotoxicosis implies symptomatic excess thyroid hormone, without referring to an etiology
• Hyperthyroidism implies excess intra-thyroidal production of hormone
• Causes for thyrotoxicosis can be divided into 1) Disorders associated with normal or high radioiodine uptake or 2) Disorders associated with low or absence radioiodine uptake

2) Normal or High radioiodine uptake

• Graves disease
• Toxic multinodular goiter
• Toxic adenoma
• Iodine induced hyperthyroidism: i.e. CT contrast or amiodarone (iodine uptake may be low in this case if exogenous iodine has a long half-life or continues to be given, as it will dilute the radioactive tracer)
• Trophoblastic disease/germ cell tumours: mediated by beta-HCG which cross reacts with TSH receptors. Examples include: hydatidiform moles/choriocarcinoma in females and testicular germ cell tumours.
• Secondary hyperthyroidism from a functioning pituitary adenoma

3) Low or absent radioiodine uptake

•  Thyroiditis:
• Pyogenic thyroiditis
• Viral thyroiditis
• Hashimoto's thyroiditis
• Postpartum thyroiditis (a form of Hashimoto's occuring postpartum)
• Radiation thyroiditis
• Palpation thyroiditis (after a surgical excision on the thyroid from it vascular bed)
• Drug induced: amiodarone, lithium

Liver abscess

Types of Liver abscess:
1) Bacterial aka pyogenic
2) Parasitic (amoebic)
3) Fungal

Pathogenesis:
1) Ascension of bacteria from biliary tree (40-50% of cases)
2) Portal vein spread (from intra-abdo source i.e. diverticulitis, appendicitis)
3) Hematogenous spread
4) Direct inoculation from trauma or surgical procedure
5) Cryptogenic

Risk factors
1) Diabetes
2) Hepatobiliary/pancreatic disease
3) Malignancy
4) Liver transplant
5) Immunocompromised: HIV/AIDS

Bugs commonly involved: mostly polymicrobia aerobes + anearobes
1) Gram positives: Staph, microaerophilic Strep, Strep milleri (abscessogenic), enterococcus
2) Gram negatives: Klebsiella, enterbacteriacea coli
3) Anaerobic: fusobacterium, bacteroides (may not be grown on culture)
4)  Fungus
5) Hydatiform cyst echinococcus: from dogs
6) Amoebic liver abscess: entamoeba histiolytica (fecal oral route)

Treatment of pyogenic liver abscess:
1) Abx to cover gram+/-/anaerobes (a penicillin, aminoglycoside/cephalosporin and metronidazole)
4) Source control: perc drainage

See the following article for more about liver abscesses Liver abscesses and Hydatid disease

Empyema

This is my catch-up blog about empyema, which we discussed on Tuesday!

1) Thoracic empyema

• Defined as pus in the pleural fluid (high PMN count) and or pH  less than 7.20. Also has high LDH due to lysis of PMNs. Progression to an empyema occurs over time and patients present subacutely with a long hx of SOB, cough etc. A dense layer of fibrin can deposit on the visceral and parietal pleurae, leading loculation and worse prognosis. This anaerobic environment leads to the proliferation of anaerobes and other bacteria.
• Common symptoms include pleuritic chest pain, dyspnea and sputum production. Those with aspiration risk, underlying lung disease, diabetics and immunocompromised are at higher risk.
• Physical exam reveals dullness to percussion, decreased breath sounds, decreased fremitus and a loss of egophony.
• Common bacteriology:
• Prevalent bacteria include: Streptococcus milleri, Staphylococcus aureus, enterobacteriaceae, strep pneumonia, GAS, CNST
• Diabetics are at increased risk of Klebsiella pneumonia
• MRSA can cause a necrotizing pneumonia that leads to complicated parapneumonic effusions. 
• The lack of anaerobic bacteria in culture does not exclude the presence of anaerobes, espcially if the fluid has a putrid odor. Empiric coverage for anaerobes should be initiatied. Common bugs include Peptostreptococcus, Fusobacterium and occasionally Bacteroides fragilus
• Don't forget tuberculous empyema, characterized by large mounts of pleural PMNs. 
• Treatment:
• Antibiotics: Should target the likely underlying cause of the pneumonia. Options for empiric therapy that cover anaerobes as well as gram + and -  include clindamycin, amoxi-clav or piperacillin tazobactam and carbapenems. 
• Sterilization of the empyema should occur within at least 4-6 wks of therapy, but therapy should be continued if there are persistent symptoms or persistent effusion as seen on imaging.
• All complicated parapneumonic effusions and empyemas should be managed with complete pleural fluid drainage. This can be done with a pig-tail or tube thoracostomy (preferred for thick loculated empyema)
• Progress should be assessed by repeat CT imaging
• Chest tubes are typically left in place until the drainage rate is less than 50mL/day and empyema cavity has closed
• If Unsuccessful, thoracics may need to be involved for a VATS (video assisted thorascopic surgery) for debridement / decortication
• Fibrinolytic agents can also be used to improve drainage of loculated effusions/empyemas. 

Cerebellar Exam

 

Yesterday we learned about how to do a neurologic exam of the cerebellum. Here is a recap for those of you unable to attend:

1) The Cerebellum 

• Coordination of volitional movements: adjusting the rate, range, force and sequence
• Motor deficits from the cerebellum are ipsilateral to the lesion, while deficits to the motor cortex of the cerebral cortex are contralateral to the lesion.
• Clinical localization in the cerebellum: The cerebellum can be divided sagitally for purposes of localization of function
• Midline: concerned with posture, locomotion, position of head relative to trunk. Midline cerebellar disease presents with disorders of stance/gait, truncal postural disturbances.
• Intermediate: Paravermal region of cerebellum. Concerned with velocity, force of volitional movements.
• Lateral: Concerned with planning of volitional movements in connection with the Rolandic region of the cerebral cortex.

2) Cardinal Signs of Cerebellar Dysfunction:

• Hypotonia
• Ataxia: defective timing of contraction of antagonistic/agonistic muscles, results in a disurbance of the smooth performance of voluntary movements.
• Dysarthria
• Abnormal ocular movements
• Tremor

3) Inspection

• Level of Consciousness
• Acute cerebellar strokes can cause raised ICP that can impair LOC
• Tone:
• Hypotonia can occur with acute cerebellar infarcts

4) Gait

• Have patient walk normally, then heel to toe (tandem gait)
• Walk is wide based, staggering, lurching.
• Lesions of the lateral cerebellum result in Patients falling towards the ipsilateral side of the lesion
• Lesions of the midline result in movements in all directions.
• Ataxia secondary to vestibular disease may appear similar (patients fall towards the affected vestibular apparatus)

5) Test of Station

• Romberg Test - Not positive in cerebellar disease (positive Romberg = patient falls). With eyes open and closed patient has a sway (towards ipsilateral side of there is a lateral lesion of the cerebellum. Visual orientation does not improve the ataxia.

6) Cranial Nerves

• Test for any bulbar abnormalities which may accompany a cerebellar stroke

7) Nystagmus

• Midline lesions: Gaze evoked nystagmus, up beat, opticokinetic, rebound nystagmus. Opsoclonus - multivectorial, fast, involuntary eye movements.
• Lateral lesions: unidirectional with fast phase towards the affected side
• Non-fatiguable

8) Speech

• Scanning, staccato, explosive speech. Unable to control volume.
• Ask the patient to take a deep breath and say "ahhhh". This tests for control of the expiratory muscles and vocal cords 
• Ask the patient to say "la, la, la" and "me, me, me" to test for rapid alternating movements of the tongue and lips.
• Ask patient to say the ABC's to assess the meter and volume of speech

9) Ataxia of the extremities:

• Ask patient to extend arms out in front and observe for tremor. Sharply tap the arms proximally and observe for oscillations of the arm as they return to baseline. The affected side has more violent oscillations.
• Test for Rebound: Ask the patient to flex their arm against your resistance, place an arm on their shoulder to protect their face. Suddenly let go of the flexed arm and observe if the patient is able to arrest the rebound of the flexed arm. Patients with Cerebellar dysfunction will be unable to do this.
• Dysmetria: abnormal excursions of movement, frequently undershooting or overshooting the target
• Tested by finger to nose testing. Must extend arm completely.
• Dysdiadochokinesia: Difficulty with rapid alternating movements
• Test with hand tapping on thigh or foot tapping
• Test with alternating fingers touching the opposing thumb.

10) Reflexes:

• Test for Pendullar reflexes with excessive sway

For more information refer to: Cerebellar exam

Nephrotic Syndrome

Today we had an excellent discussion about a 61 yo Female who presented with an acute onset of anasarca and nephrotic range proteinuria with a normal serum creatinine.

There are three major causes of nephrotic syndrome:

1) Minimal Change Disease

• Epidemiology: Most common in children, but has bimodal distribution. 
• Clinical presentation: sudden onset (days to weeks) of nephrotic syndrome. Can also have microscopic hematuria. Usually have normal serum creatinine. In elderly, often present with hypertension.
• Etiology:
• Idiopathic
• Drugs: NSAIDS (most common), antibicrobials (ampicillin, rifampicin, cephalosporins), Lithium, Penicillamine, sulfasalazine, Trimethadione, gamma interferon
• Neoplasms: Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia
• Diagnosis:
• Given the high prevalence of MCD in children, a diagnosis can often be made without a renal biopsy. 
• In adults, often a renal biopsy is needed to distinguish from other causes of nephrotic syndrome.
• Treatment:
• Very steroid responsive, 80-90% achieve complete remission. Takes longer in adults than children. up to 75% respond within 6months.
• Relapses are harder to treat, and may require cyclosporin.
• In conjuction with: Low salt diet, diuretic, ACEi

2) Focal Sclerosing Glomerular Sclerosis:

• Clinical Presentation: Gradual onset of nephrotic syndrome, can have microscopic hematuria
• Etiology:
• Primary FSGS: idiopathic cause of nephrotic syndrome (mediated through circulating permeability factors, increasing the permeability of the glomeruli to albumin). 
• Secondary: Viruses (HIV, Parvovirus B19, hepatitis C, EBV, CMV), drugs (IV pamidronate, anabolic steroids, interferon), obesity, lupus, reflux nephropathy, hypertensive nephrosclerosis.
• Diagnosis:
• Biopsy shows Segmental areas of mesangial collapse and sclerosis. Collapsing FSGS (HIV, iv pamidronate) characterized by collapse and sclerosis of entire glomerular tuft.
• Treatment:
• Responds to steroids, but is less responsive to steroids than MCD. For steroid resistant or relapsing disease, cyclosporine is commonly used.

3) Membranous Disease:

• Clinical Presentation: Gradual onset of nephrotic syndrome, can have microscopic hematuria
• Etiology: Solid organ tumours, lupus - class V lupus nephritis (does not need to be accompanied by other disease manifestations of lupus), infections (Hepatitis B, syphilis), Drugs (penicillamine, gold, NSAIDS)
• Diagnosis: 
• ANA, C3/4, Hepatitis serology, 
• Biopsy shows: Thickening of the glomerular basement membrane, in absence of hypercellularity.
• Treatment
• Control BP, ACEi, diuretic
• Prednisone +/- cyclophosphamide or cyclosporin

For more information refer to the following great articles on Nephrotic syndrome:

Nephrotic Syndrome, New England Journal of Medicine, 1998

Attending Rounds: An older patient with Nephrotic syndrome CJASN

A case of bloody diarrhea

Today we discussed a case of bloody diarrhea here are some pearls:
1) Definition:

• Bloody Diarrhea = Colitis
• Triad of bloody diarrhea, lower abdominal pain and fever = "Dyssentry"

2) Etiology:

• Infectious: Salmonella, Shigella, Yersinia, Campylobacter, C. difficile (though rare), E. coli (enterohemorrhagic O157:H7), CMV in immunocompromised hosts. The most common causes in Toronto would be campylobacter
• Ischemic: Embolic (a. fib, cardiogenic emboli), mesenteric vein thrombosis, aortoiliac bypass, cardiopulmonary bypass.
• Inflammatory: Inflammatory bowel disease, vasculitis of the gut
• Radiation colitis

3) History:

• Exposure history: 
• Travel/sick contacts
• Food: raw beef, pork, poultry, alfalfa sprouts (E.coli), rice (B. cereus), unpasteurized dairy
• Timing of onset: less than 6hrs likely from pre-formed toxin, 8-16h think clostridium, more than 16hrs think viral or bacterial infection, if starts as diarrhea and progresses to h/a, myalgias, think listeria (especially in pregnant women)
• Medications: recent abx
• Recent hospitalizations
• Hx of IBD, radiation, immunosuppression
• Extra-intestinal manifestations of IBD
• Sexual hx

4) Diagnosis:

• Stool C + S, C. diff PCR - very sensitive and specific
• Stool O + P - not very cost effective, but reasonable in immunocompromised patients, community outbreaks of giardia or cryptosporidium, chronic diarrhea.
• Stool leukocytes - not very helpful

5) Treatment:

• Supportive!
• IV hydration, replete electrolytes (patients often have Non-Anion Gap Metabolic Acidosis initially)
• Should you treat with Antibiotics?
• Impact is modest: Decreases duration of symptoms by several days
• Consider treatment in people at risk for complications: elderly, diabetics, cirrhotics, immunocompromised
• Antibiotics are indicated for ETEC (fluoroquinolone), C. diff (metronidazole), Salmonella (flouroquinolone). Abx can also be used for severe campylobacter (macrolides or flouroquinolone)
• See the following link for Utility of antibiotics in diarrhea
• HUS: caused by the shiga toxin from E.coli O157:H7 characterized by bloody diarrhea, MAHA, thrombocytopenia, acute renal failure +/- neurologic symptoms. Antibiotics have been shown to prolong diarrhea and lead to worse outcomes. Prognosis is better than TTP.

Does my butt look firm... or inflammed?

Complications of Polymethylmethacrylate injections

1) What is it?
PMMA is a synthetic material that was first synthesized in 1902 and patented as Plexiglas in 1928. It was initially used in the medical field as bone cement but has gone on to have multiple different uses, including intra-ocular lenses and vertebroplasty. Given its smooth surface, chemical innertness and biocompatibility it has become popular as a dermal filler in cosmetic procedures. There are many commercial fillers containing PMMA, differing in terms of the size of the PMMA spheres and the suspension.


2) How does it work?
PMMA is injected into the dermis. Initially after implantation there is an acute macrophage mediated inflammatory reaction. Permanent results occur when macrophages convert into epitheliod cells that replace the suspension material with fibrin and eventually collagen. However, in a small percentage of cases (pharmaceuticals state less than 2.5%) a nodular granulomatous reaction can occur.

3) Complications:
A study out of the University of Sao Paulo documented and described 32 cases of complications due to PMMA.

• Tissue necrosis: can occur immediately. Caused by disruption of the vascular supply, by injection or compression on vessels.
• Delayed type sensitivity to bovine collagen plus PMMA, has been documented 6-24 mo post injection.
• Granulomas: occurred 6 months - 1 year post injection. Characterized by localized pain and nodules at the site of injection.
• Chronic inflammation: 1-10yr post injection. Characterized by cyclic pain and swelling.
• Local infection: can occur immediately and has been documented up to 1 yr post injection.

Some food for thought next time you consider joining a PMMA party...

Complications of PMMA injections

Autoimmune Polyglandular Syndrome

Yesterday we talked about an interesting case of a young male with a history of Type I DM and Celiac disease who presented with severe hyperkalemia (8mmol/L), hyponatremia, hypotension and non specific abdominal complaints.

With that degree of hyperkalemia and his history of multiple autoimmune diseases, the working diagnosis was primary adrenal insufficiency and possibly Polyglandular Autoimmune Syndrome type II.

1) Autoimmune Polyglandular Syndrome type I (AKA Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy APECED)

• Hypoparathyroidism
• Chronic mucocutaneous candidiasis
• Primary adrenal insufficiency (Addison's disease)
• hypogonadism
• Malabsorption and other gastrointestinal disorders

2) Polyglandular Autoimmune Syndrome type II (much more common)

• Type I DM
• Autoimmune thyroiditis, occasionally Graves disease
• Primary adrenal insufficiency
• Secondary adrenal insufficiency from autoimmune hypophysitis
• Hypogonadism
• Non-endocrine autoimmune phenomenon (vitiligo, myasthenia gravis, TTP)
• Schmidt's syndrome: primary adrenal insufficiency and autoimmune thyroid disease

Fever in the Immunosuppressed Patient

Today we talked about fever in a patient with a history of AML after completion of chemotherapy. We spoke about the importance of maintaining our natural barriers (mucosal, skin, nails) in defence of pathogens. Here are some important points we touched on:

1) Types of immunity:

• Innate: 
• Parts of the immune system able to respond to insults immediately, not reliant on antibodies or other acquired mechanisms
• Acquired:
• Cellular: Mediated largely by T cells. Important for intracellular pathogens (mycobacterium, fungal infection, viruses, some bacteria, parasites)
• Humoral: immunologic responses mediated by antibodies (from B-cells and T helper cells) Important for defence against encapsulated bacteria
• Our patient had AML with post chemotherapy bone marrow suppression and severe neutropenia. Therefore she had suppression of both her innate and acquired immune system.

2) Mucositis/Esophagitis

• Bacterial translocation: 
• Gram positives: Strep viridans and milleri. The S. milleri group can survive under low oxygen tension and is "abcessogenic"
• Anaerobes: Fusobacterium (associated with internal jugular thrombophlebitis AKA Lemierre's syndrome)
• Gram negatives: institutionalized/sick patients may develop colonisation of the Upper GI tract with lower GI tract commensals, putting them at risk of gram negative bacteremia. Consider Pseudomonas aeruginosa, Enterobacteriacea, Enterococcus.
• Fungal
• Candida
• Fluconazole: activity limited to yeasts and some endemic fungi (histoplasma, blastoomyces, coccidioides and paracoccidioides). Excellent activity against Candida albicans, but less against non-albicans.
• Itraconazoel: Broader spectrum than fulconazole. Including endemic fungi, sporothrix schenckii and aspergilus.
• Voriconazole: enhanced activity against aspergillus and other hyalohyphomycoses. Superior to fluconazole resistent C. glabrata dn C. krusei.
• Posaconazole: expanded spectrum with activity against mucorales, yeasts and molds.


• Viral
• HSV, CMV

3) Aspergillosis

• Invasive aspergillosis: Diagnosis based on culture of aspergillosus with histopathologic evidence of invasive hyphae or culture from a normally sterile site. Galactomannan or Beta D glucan assay can also be used to determine invasive aspergillosis.
• Chronic pulmonary aspergillosis: Four types: aspergilloma, chronic cavitary pulmonary aspergillosis, chronic fibrosing pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis.