Academic Day Seminar – HIV

I really enjoyed this session by Dr. Sandra Chang! 🙂 I thought she provided a very practical and comprehensive overview on HIV and did an excellent job in helping us form an approach to managing patients with HIV!

Some key points from this session are:

  • Initial therapy consist of triple drugs – combining medications for different HIV targets helps decrease the risk of resistance…but also requires pts to be able to commit/adhere to a regimen. Assess and help address any barriers!
    • Ensure seamless administration with 100% adherence with good tolerability:
      (1) Continuing from home
      (2) While in hospital
      (3) On discharge
  • Drug interactions – consider ALL types of medications, including street drugs
    • Useful resources: liverpool, HIVclinic
    • Lexicomp: not the most accurate, but can be used for comparison with above resources
      • Do not use lexicomp for renal dose adjustment!
    • RAL has more data in chemo DDIs, but DTG likely tno expected to interact with chemo

 

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Academic Day Seminar – Total Parenteral and Enteral Nutrition

This was a really great session to have, and Jan did an absolutely terrific job going over this large topic and giving us practical take-away points on nutrition. This was definitely a very heavy topic and I’m glad I have a TPN rotation to try to apply the knowledge and concepts from this session.

I. The Basic Five for Enteral and Parenteral Nutrition:

  1. Equations
  2. Monitoring
  3. Tube/Access
  4. Delivery
  5. Formula

II. When you have the choice to decide between TPN and EN, EN is the 1st Choice!

  • Enteral Nutrition does not necessarily have lower risk than TPN
  • Risks of EN include:
    • Aspiration pneumonia (inability to protect airway)
    • Tube placement complications (e.g. perforation of GI tract)
    • Tube maintenance complications (esp with enteric tubes which migrate upwards and feeds to esophagus, potentially leading to aspiration)
    • GI intolerance
    • Inadequate intake (mean % received is usually 60% of what is prescribed)
    • Drug interactions (e.g. phentoin)
  • Risks of PN include:
    • Infectious complications (e.g. line infections)
      • Risk is now lower with better glucose control and stricter criteria to decide who gets PN
    • Catheter-related complications
    • Higher risk of refeeding syndrome (risk is still present with EN but with PN tend to be more aggressive with refeeding so risk is higher)
    • Liver dysfunction (PNALD = Parenteral Nutrition Associated Liver Disease)
    • Fluid/electrolyte/glucose imbalance (as increased tendency to be more aggressive with refeeding)
    • Gut mucosal atrophy (PN does not contain glutamine and GI is not being used)

✔ Enteral Nutrition

What are some barriers to providing EN?:

  • Developing procedures for safe EN practice
  • Thought that tube feeds cause diarrhea
  • CHIME: Constipation, History, Infection, Medications, Equipment

EQUATIONS:

I. Energy

  • Factors that ↑ metabolic rate: lean body mass, physical activity and exercise, growth and development, being male, height (overall size), digestion)
  • Factors that ↓ metabolic rate: aging, fat mass (which is not metabolically active), starvation and dieting, sedentary living, being female (due to less muscle mass), sleep
  • % REE (= resting energy expenditure): as injury escalates (e.g. elective surgery → skeletal trauma → sepsis/peritonitis → major burns), the REE and metabolic response increases ..and when patients are in starvation, % REE decreases
  • Depends on the goal, which is usually: weight maintenance (vs. gain or loss)
  • Predictive equations: accuracy rate of 40-75% (compared to IC)
    E.g. Harris Benedict, Ratio Method
  • In ICU: Indirect calorimetry
  • What weight to use?:
    Adjusted body weight – highly debated in literature
    ADJ W = ((ABW-IBW)x25)+*IBW
    *Use BMI 25

II. PROTEIN:

  • Calculating protein needs:
    Most patients require 1.2-1.5g/kg/d of proteins, 20% total kcal

III. FLUID:

  • Multiple points of interface with water:
    1. Hydration, 2. Flushing EAD, 3. Dilution (medications, powdered formula)
  • Methods:
    • mostly done by age:
      20-55 yo: 35 mL/kg/day
      55-75 yo: 30 mL/kg/day
      >75 yo: 25 mL/kg/day
    • but this is just a starting point and will have to think of other IV fluids, current volume status, etc.
  • None of the formulas have been validated against a gold standard. No recommendations. Closely monitoring patients for optimal water intake regardless of which formula is chosen!

Tubes:

  • No tube = No nutrition (since no access)
  • No tube = No medication

NOMENCLATURE:

Nasoenteric Tubes: Insertion site: Nose → GI tract

  • Irritant to nose…and risk of fistulas due to exposure of feeds
  • Nasogastric tube
  • Nasoduodenal tube (post-pylori)
  • Nasojejunal tube (post-pylori)

Enterostomy: Insertion site: GI tract → GI tract

  • Gastrostomy: Stomach → Stomach
  • Jejunostomy: Small bowel → Small bowel
  • Gastrojejunostomy: Stomach → Small bowel

Endoscopic Placement:

  • PEG: Percutaneous (through the skin) Endoscopic Gastrostomy
  • PEG-J: Percutaneous Endoscopic Gastro-jejunostomy
  • PEJ: Percutaneous Endoscopic Jejunostomy

Radiologic Placement:

  • PRG: Percutaneous radiologic gastrostomy
  • PRG-J: Percutaneous radiologic gastrojejunostomy
  • PRJ: Percutaneous radiologic jejunostomy

Radiologic vs. Endoscopic Placement: both equally successful (90-95%) with low mortality rates

SIZE TUBES FOR NG:

  • anything less than French 12 should NOT be used for medications (d/t occlusion)
  • French 8 vs 12 = no difference in comfort for patients
  • MEDS ⇒ FRENCH 12
  • Internal diameter ~ External diameter

SIZE TUBES FOR ENTEROSTOMY TUBES:

  • want larger diameters
  • need to allow tract to mature and form nice fistula tract (textbook typically states ~2 to 4 weeks but in reality it usually takes 4 weeks and might be longer for pts with impaired wound healing like diabetes)

HOW TO DECIDE WHICH TUBE?:

Tube feeding routes:

  • Insertion site: Expected duration
    – if longer duration, should be away from nostril
    – enterostomy tubes: tend to be larger bore tubes
  • Terminus: Gastric function

Orogastric tubes: insertion site is mouth

  • Indication: trauma to nostril, sinus issues
  • more commonly seen in ICU (and some evidence suggesting decreased risk of VAP, but weak evidence)
  • if patients are conscious…may chew on the tube…but in ICU, use oroendotracheal tube which are larger and harder to chew

If < 4-6 weeks:

  • GASTRIC → NG (gastric) tube
  • If Gastric contraindicated (e.g. gastric stasis) → ND tube
  • CI: surgically altered gastric anatomy, delayed gastric emptying, GERD, increased aspiration risk, gastric outlet or duodenal obstruction, gastric or duodenal fistula

If 4-6 weeks:

  • GASTRIC → G (gastrostomy) tube
  • If gastric contraindicated → GJ tube or J tube (tube tip lies depending on whether the stomach is emptying)
  • Basal gastric acid secretion: 2.4-3L per 24 hrs
    • if patient has obstruction pre-pyloric, patient will be vomiting this ..so you would want a tube tip to lie in J tube and a port in the stomach to decompress and get rid of acid

DELIVERY:

Delivery schedules: Important to know for dosing of medications!

  1. Continuous: run over 24 hours (start at lower rate and then titrated)
  2. Cyclic: a set rate that runs over less than 24 hours (usually a term used for nocturnal feeding…feed during night and disconnect during the day…may be because don’t want to be hooked up all day…or nocturnal feeds may be a supplement)
  3. Intermittent: larger volume of feeds delivered over shorter time (~1-2 hrs) (e.g. given at meal times)
  4. Bolus: similar to intermittent…taking larger volumes of feed delivered over a SHORTER time (~20 mins)

Most patients will be getting continuous delivery as possible fluid/electrolyte disturbances, gastric stasis and/or hemodynamic instability make more rapid administration potentially hazardous

Drug interactions:

  • Phenytoin
  • Ciprofloxacin

Dieticians don’t like post-pyloric tubes as cannot tolerate large volumes over a short time (e.g. diarrhea)

PICKING FORMULASEfficacy studies not required before products can be manufactured

  • Classifications: polymetric (everything is intact → fluid, fiber, protein), disease-specific, modular

When should a fluid restricted formula be used?

  • Renal dysfunction
  • RFS risk
  • Liver compromise
  • Cardiac compromise
  • Post-op fluid retention/redistribution

When should a fibre containing formula be used?

  • Fibre = good to help GI tract and lyte absorption…but not a lot of evidence
  • Insufficient data to support routine use of fiber in critically ill pts. Concerns re how fibre might be associated with harm in some pts (hemodynamically unstable, bowel ischemia risk, suppressed bowel motility)

When would a higher protein formula be used?

  • Depends on the patient’s injury

Disease-specific:

  • there are renal products (low protein) for CKD who are not on dialysis
  • for pulmonary compromise (e.g. someone intubated), high fat low carbohydrate = more CO2 is generated with carbohydrate → but evidence is weak
    – main thing is to not overfeed the patients
  • for hepatic products (e.g. encephalopathic patients) → have to show that correct fluid/lyte balance, metabolic stress, maximum therapy e.g. lactulose → if encephalopathic then may be a role for these products (removed from formulary at VGH)
  • for diabetic products: less carbohydrate and higher fibre with fat → this helps to slow gastric emptying…but no evidence supporting efficacy

MONITORING:

Mnemonic: Good Monitoring Methods Improve Nutrition

  • GI: abdominal distension constipation, diarrhea (even for patients on PN since you want to know when we can use the gut, for example in patients who were put on PN d/t ileus)
  • Metabolic
  • Mechanical
  • Infection: tube site
  • Nutrition: mean % prescribed, ins and outs (e.g. feeds are held due to medications)
    • Do not look at albumin (since negative actue phase reactant and a measure of ILLNESS and not nutrition)
    • Do not look at weight (since measure of hydration)

DIARRHEAB5 JG Diarrhea 2017 final

TUBE OCCLUSION:

Potential causes include:

  1. Poorly crushed meds
  2. Liquid meds with low pH – the pH of the formula is ~ 7…therefore, if a protein rich environment = causes precipitation of protein and occludes the tube…so liquid medications may not always be better (as well ingredients like sugars, preservatives, thickening agents can cause significant SEs)
  3. Viscious liquid medications
  4. Failure to flush tube before/between/after medications are given

Prevention includes:

  • Never add meds directly to feed or bag
  • If there is both a G and J port present, use the G port for meds
    (e.g. for dual lumen tubes – 1 lumen terminates in J port and 1 lumen terminates in the G tube for decompression)
    …if gastric stasis has resolved, and gastric emptying has improved = would want to use the G port since it is the larger bore and it is more physiologically better to access medications
  • If tube lumen < 12 Fr. Do not use for meds
  • Always flush medications

REFEEDING SYNDROMEB5 EN RFS Monitoring March 2017

  • period of under nutrition, associated with fluid and electrolyte shifts and metabolic complications
  • Electrolyte replacement – consider comorbidities (e.g. renal failure pt)
  • For extreme risk at RLS (need to go slow with nutrition) to provide more time to replete electrolytes
  • Thiamine: water soluble (few stores in our body…can be depleted within 11-21 days)
    • deficiency: Wernicke’s encephalopathy (200-300mg daily)

Possible contributing factors of underfeeding:
1. Incorrect energy calculation
2. Too infrequent monitoring
3. Incorrect formula
4. Feed delivery interruptions (e.g. medication delivery)

If EN is to be held for meds, can consider:
1. PAD EN rate for time off pump
2. Consider switching to nocturnal feeds if drug dose during the day as BID or QID doses
3. Discuss with pharmacist re reduced drug dose frequency
4. Change to more energy dense formula

Other references:


✔ Total Parenteral Nutrition

  • KEY POINT: PRO 20%, CHO 50%, LIPID 30%
    • These % are generally safe as they will land you in between minimum and maximum dose
  • Average length: 6-10 days of TPN
  • Indications:
    • malnourished or at risk for malnutrition
    • contraindication to EN
    • patient cannot tolerate adequate EN
    • lacks sufficient bowel function to maintain or restore nutrition status due to GI dysfunction

Contraindications to EN:

  1. Severe hemodynamic instability
  2. Prolonged ileus, vomiting, diarrhea or persistent GI bleed
  3. Bowel obstruction
  4. Significant GI ischemia
  5. High-output fistula (if fistula that is gastric/small-bowel → can still enterically feed the patient by bypassing..but if too far down the GI tract where not enough surface area…may have to give it up)

Reasonable time frame for initiating PN when EN is not feasible in ADULTS:

  1. Initiate PN after 7 days for well-nourished, stable patients who have been unable to receive significant (>50% est requirements) oral or enteral nutrients
  2. Initiate PN within 3-5 days in those who are nutritionally at risk and unlikely to achieve desired oral intake with EN
  3. Initiate PN as soon as is feasible for patients with baseline moderate or severe malnutrition in whom oral intake or EN is not possible or sufficient
  4. Delay the initiation of PN in a patient with severe metabolic instability until the patient’s condition has improved

PRO, CHO, LIPIDS:

I. Protein:

  • Provide substrate to support organ structure/function; promote wound healing; support immunity
  • Energy value (same as enteral): 4kcal/g

II. Carbohydrate:

  • Source of energy
  • Composition: Dextrose monohydrate
  • Energy value: 3.4kcal/g
  • Min: 100g/d (for main organs  – e.g. CNS)
  • For peripheral access, higher mosmol/L = increased risk of thrombophlebitis
    For central access, osmolality is not an issue = can see D20W and D50W

III. Lipid injectable emulsion or ILE

  • Provides essential fatty acids and energy
  • Several types commercially available
    Differ in:
    1. Percent emulsion: 20%, 30%
    2. Type of oil: soybean, olive, other
  • Long chain omega acids thought to be immunosuppressive…but…as critical ill patients are malnourished…don’t worry too much about that

Electrolytes: requirements vary with: body weight, nutritional status, degree electrolyte depletion, organ function, ongoing electrolyte losses, acid/base balance, medications, disease process, carbohydrate composition

Nutrition – With refeeding syndrome, always start at LOWER doses (e.g. if patient needs 2000 cal → will give 1000 cal and then follow the PRO 20%, CHO 50%, LIPID 30%  = no issue even though carbohydrate drives refeeding syndrome more since will be at lower dose)

  • Most products are transitioning to not contain electrolytes
    (the values listed on the basic 5 facts are based on a healthy individual)
  • Managing short term electrolyte deficits by addition to the PN solution is not ideal
    • baseline/maintenance lytes (if needed) should be in TPN
      But…when in doubt, leave it out!
  • Electrolytes can be lost in NG suction!

Thiamine + Vit C: not unusual to add on additional thiamine and Vit C

  • FDA recommended that not enough vitamin C in products
  • Usually add on additional 100mg Vit C and 100-300mg Thiamine

Trace elements:

  • FH + VCH: Use Micro + 6 Concentrate
  • In short-term, standard is okay..but in longer term, concern about accumulation in trace elements especially in patients with altered liver dysfunction (but generally rare to not see the standard amounts of trace elements)
  • Iron not routinely added to PN solutions (as not stable and concern about infusion reactions)
  • PPN: Osmolarity < 900 mOsmol/L, limit 14 ds, have to rotate site
  • CPN: highly concentrated hypertonic solutions, may be used indefinitely

Compounding – PN product type:

  • Commerical pre-mixed: solution (lipid, CHO, PRO) and each macronutrient is kept in a separate entity…roll the bag and break membranes and get a 3 in 1 and with standard electrolytes for ~70kg
    – can add additional electrolytes and trace elements
  • Standard compounded
  • Custom compounded

!!Appropriate monitoring parameters shall include!!:

  • Fluid requirements
  • Serum electrolyte concentrations
  • Serum glucose concentrations
  • Hepatic function
  • Renal function
  • Serum triglycerides
  • Signs/ symptoms of access device complications

FYI: In pts with Anorexia Nervosa – albumin will be normal (as pt has adjusted)

  • if hit by truck = catecholamine response and for sick pts → albumin will be low

Acid-base:

  • Potassium chloride and potassium acetate
  • Before adjusting the PN, what would you adjust?
    • If IV running…and then PN gets started and nobody has written TFI “Total Fluid In”… so if NS running where Cl: 154 mmol/L is going in → causing acid-base disorder

Impact of overfeeding with PN (since bypassing GI tract)  PNALD

  • Altered LFTs common
    • other factors can also affect liver dysfunction: sepsis, meds, etc.)
  • Lack of oral intake or EN: not stimulating gall bladder contraction to release bile
    • increase risk of stones
  • PNALD typically improves with the advancement of EN and discontinuation of PN
    • e.g. can we start trickling feeds to allow for stimulation of gall bladder and biliary tract
  • Some evidence that long-term soybean-based IVFE = increased risk with PNALD
    • Intralipid emulsion = starting to be taken off formulary (d/t liver concerns)
  • Some evidence that continuous PN is not physiologically normal and may be affecting liver function → may go with cyclical to give liver a break

PNALD + RLS: Less is MORE

Academic Day Seminar – Anti-fungals

I can’t believe it’s our last resident-led ADS. Julianna and Rob did a great job facilitating the session! They provided many clinical pearls and an excellent overview on anti-fungals!

My notes can be found here: Antifungal 2017 ADS Notes

Important tidbits to keep in mind when approaching anti-fungal infections:

  • Amphotericin B
    • Achieves high levels in kidney, primarily stored in kidney and slowly released (= long terminal half-life ~ 15ds) –> potential for renal toxicity (hypoMg, hypoK, and eventually renal tubular acidosis)
    • Liposomal Amphotericin B – ↓ nephrotoxicity, ↓ incidence of infusion reactions
      • At VGH and most other BC sites…tend to use liposomal right off the bat due to concerns with nephrotoxicity, regardless of baseline renal function
      • Deoxycholate has poor CNS penetration, Liposomal may have better CNS penetration and would be the alternate formulation in CNS aspergillosis
  • Flucytosine
    • *SAP* Indication for cryptococcal meningitis in combination with Amphotericin B
    • Possibly de-aminated to 5-FU (might be cause of bone marrow suppression and GI intolerance)..also causes hepatic suppression
  • Voriconazole – Candida, Aspergillus
    • Non-linear kinetics – half-life ~6 hrs (VARIABLE)
    • Hepatically metabolized by CYP2C9, 2C19 and 3A4
    • + Inhibits the above enzymes 2C9, 2C19 and 3A4
  • Itraconazole – role is limited due to moderate F, poor distribution…but has a broad spectrum of activity and may serve as salvage therapy for patients who have not recovered on other azoles
    • Posaconazole – “improved version of itraconazole” – and roles includeProphylaxis of invasive fungal infections in neutropenic patients, Refractory invasive fungal infections, Zygomycetes
  • Activity – triazoles (fungistatic to yeasts, fungicidal to aspergillosis); echinocandins (fungistatic to aspergillosis, fungicidal to candida)
  • Echinocandins – all highly protein bound, distributes well into tissues but has NO CSF penetration
    • large molecules = difficult to cross through CNS = won’t use for CNS infections
  • Therapeutic drug monitoring for flucytosine, voriconazole, posaconazole
    • Voriconazole + posaconazole levels sent to SPH (done once weekly)
  •  *remember to renally adjust* – Flucytosine, Fluconazole
    • Risk of toxicity via accumulation of IV vehicle in voriconazole in renal impairment – if appropriate, change to PO voriconazole
    • ?adjusting for renal dysfunction for amphotericin B – complicated
  • Do not consider candida as a contaminant in BCx (even if 1/4 or 2/4 +, would still treat)
  • SAP drugs – Isavuconazole, Flucytosine

Academic Day Seminar – Feb 10

✔ ECGs!

This was a very fun and interesting session, and I really enjoyed working through the ECGs using the systematic approach that Dr. Loewen taught us. I still find it challenging to read ECGs, especially ones that are not very clean or straightforward, but will aim to avoid reading the interpretations on the top of the ECG and developing this skill in future rotations!

Some key points from this session:

  • Before reading an ECG: check the date, time and patient
    • Correlate why the ECG was done, and root it to their story (e.g. symptoms, PMH)
  • Orientation to a 12 lead ECG:
    • X-axis: small box → 0.04 secs; large box (x5 small) → 0.20 secs
      • 4 sections of 2.5 seconds
      • Picture of the atria and ventricles simultaneously!
    • Y-axis: voltage/electrical activity
    • Leads: not electrodes; each electrode picks up a signal from the heart and leads are specific combinations of those signals
      = record tracing of electrical activity between two electrodes
    • Precordial (chest) leads: V1-V6; Limb leads: I-III, aVL, aVF, aVR
    • Anterior leads: V1 – V4
      • V1: closest to the RIGHT atrium
      • These make sense as “anterior” leads → think of location of the leads (see pic below)!
      • V2-V4: closest to the LEFT ventricle
        Anterior MI: Fatal kind of MI since affecting L ventricle
    • Lateral leads: I, aVL, V5-V6
    • Inferior leads: II, III, aVF
      • Looking from bottom to top → RIGHT ventricle (but not completely)
      • If signs of ischemia in these leads → add 3 leads to posterior to check for a posterior MI
    • aVR → doesn’t tell you anything (wa wa wa)
    • Rhythm strip: usually either lead II or V1 → 10 seconds long
    • Contiguous: if they are assigned to the same anatomic group (e.g. STEMI in 2 inferior leads, 2 anterior leads, etc.) or for a STEMI, contiguous is also referring to 2 numerically contiguous leads (V1-V6)
What each Lead “sees”
Leads Heart Surface Viewed
II, III, aVF Inferior
V1, V2 Septal
V3, V4 Anterior
I, V5, V6, aVL Lateral

Reference: 12 lead ECG pocket reference 

  • 6 step approach for ECG interpretation for Pharmacists: RATE, RHYTHM, CONDUCTION, AXIS, HYPERTROPHY, INJURY/ISCHEMIA/INFARCTION

1. Rate

  • Tricks to calculating the rate without reading the computer’s calculation:
    (1) Use the rhythm strip + multiply the # of QRS complexes seen by 6 (=60 secs)
    (2) 300/150/100/75/60/50 rule for each large box

2. Rhythm

  • Identify if Normal Sinus Rhythm (NSR) or Sinus Rhythm (SR)
    • SR: every P is followed by a QRS, and every QRS is preceded by a P
    • NSR: SR + bpm: 60-100
      • Tachycardia =/= NSR
      • Bradycardia =/= NSR
      • SR + PVCs =/= NSR
  • If not in sinus rhythm, identify arrhythmia
    • Atrial Fibrillation: no visible P waves (II + V1)  + R-R instability
      • R-R instability may be difficult to see if HR is elevated…may have to slow patient’s HR to definitively conclude AFib
    • Atrial Flutter: saw-toothed Ps, fixed A-V conduction ratio
    • Heart blocks (AV node is blocked):
  • 1st degree heart block → often the GoT for AV nodal blocking tx
    • PR > 200msec (more than 1 large box) + no skipped beats
    • Would not be able to see 1st degree heart block in Afib
  • 2nd degree heart block
    • Mobitz I “Wenckebach”: PR interval gets progressively longer until atrial impulse is not conducted and QRS drops
    • Mobitz II: PR interval is constant (not necessarily >200msec) and atrial impulse is not conducted and QRS drops
  • 3rd degree heart block: COMPLETE heart block → dissociation between atria and ventricles
  • PVCs: http://lifeinthefastlane.com/ecg-library/basics/pvc/
    • Broad QRS complex > 120 msec
    • Premature
    • Discordant ST segment and T wave changes (e.g. directed opposite to main vector of QRS complex)
    • Usually followed by a full compensatory pause
    • Retrograde capture of the atria may or may not occur (e.g. inverted P wave)
  • VT: Rate >120 + >2 wide QRS complexes in a row
    • can progress to Vfib
  • VFib: http://lifeinthefastlane.com/ecg-library/ventricular-fibrillation/
    • Chaotic irregular deflections of varying amplitude
    • No identificable P waves, QRS complexes or T waves
    • Rate 150-500 bpm
    • Amplitude decreases with duration (coarse VF → fine VF)

3. Conduction

  • PR: conduction from atria to ventricle
  • QRS: width is attainable in every lead even if it may look different
    • Helps identify wide complex arrhythmias (e.g. Vtach)
  • QTc:
    • What you see on the ECG for QT is often higher than corrected QTc (which is corrected by the R-R interval)
    • Risk of torsades increases significantly after 500msec
      → risk of non-perfusing arrhythmia
  • If give anti-arrhythmics, there is also a risk of arrhythmic death

4. Axis: mean vector of depolarization for ventricles

  • Normal “R” axis : -30 to + 110
  • L axis deviation (less than -30): sign of LVH and/or R ventricular ischemia
  • R axis deviation (more than 110): sign of RVH and/or L ventricular ischemia
    • Causes of RVH: cor pulmonale → pulmonary HTN (primary + secondary), congenital heart defects, pulmonary fibrosis (incl. caused by COPD)
  • If normal axis, doesn’t necessarily mean that have no LVH/RVH or ischemia but may be a result of a “mixed” picture

5. Hypertrophy

  • ECG = not diagnostic of hypertrophy → ECHO = diagnostics
  • Atrial  Hypertrophy (Look at V1): Bi-phasic P waves
    • E.g. clinical significance: atrial hypertrophy = risk factor for unsuccessful cardioversion
  • LVH: S wave in V1 + R wave in V5 > 35 mm (low sensitivity, high specificity)
  • RVH: Poor R wave progression (decrease in size) from II → III → aVF
  • Injury/Ischemia/Infarction: can be acute or permanent findings
    • Inferior → Anterior → Lateral → Posterior (if huge R wave in V1 would do posterior leads V5R, V6r, etc.)
    • Ischemia:
      Usually see 1st flipped Ts → ST depression → ST elevation (any point during this, you can see pathological Q waves)
    • Look for 5 things:
      1. T wave inversion = FLIPPED Ts
      2. ST depression > 1mm
      3. ST elevation > 1mm
      → remember that you have electrodes all over the body, and some are going to see the STEMI from the opposite perspective = reciprocal changes
      → E.g. a + electrode sees the STEMI head on and may produce ST elevation…but a different lead saw the STEMI from the opposite perspective, then it might demonstrate an opposite set of changes or ST depression
      4. Q waves: http://lifeinthefastlane.com/ecg-library/basics/q-wave/
      – negative deflections preceding a R wave (without a + deflection = R wave before it)
      → pathological and non-pathological Q waves
      → pathological Q waves: WIDE (>1 box in width) and/or DEEP/BIG (larger than 1/4 of the R wave or 1/3 of entire QRS complex)
      → if width is 0.04 s or more, suspect the Q wave to be pathological and possibly ECG evidence of dead myocardial tissue
      → Q waves: If see Q waves with no acute s/s of infarction → “Old inferior MI/infarct” → “age undetermined”
      → BUT..seeing pathologic Q waves does NOT mean that the STEMI is over and has run its course
      5. BBB: always have QRS widening since the R or S waves are splitting
      → look for splitting of R or S waves
      – makes it difficult to interpret and find the above 4 things
      e.g. – if have BBB and ST elevation, can’t call it a ST elevation since the BBB is affecting the ST segment → cannot diagnose ACS in BBB patients = need to rely on other diagnostics (e.g. trop, clinical presentation)
    • More profound MI: ST elevation + Q waves
      Less profound MI: ST depression + T wave inversion

Useful Diagrams:

 jpoint.jpg

Screenshot 2017-02-11 12.32.46.png

Screenshot 2017-02-11 19.52.33.png

Location of a Myocardial Infarction (Ref: Pocket Guide):

Location of MI Indicative Changes (leads facing affected area) Reciprocal Changes (leads opposite affected area) Affected (Culprit) Coronary Artery
Anterior V3, V4 V7, V8, V9 Left coronary artery

·         LAD – diagonal branch

Anteroseptal V1, V2, V3, V4 V7, V8, V9 Left coronary artery

·         LAD – diagonal branch

·         LAD – septal branch

Anterolateral I, aVL, V3, V4, V5, V6 II, III, aVG, V7, V8, V9 Left coronary artery

·         LAD – diagonal branch and/or

·         Circumflex branch

Inferior II, III, aVF I, aVL Right coronary artery (most common) – posterior descending branch or
Left coronary artery – circumflex branch
Lateral I, aVL, V5, V6 II, III, aVF Left coronary artery

·         LAD – diagonal branch and/or

·         Circumflex branch

Right coronary artery

Septum V1, V2 V7, V8, V9 Left coronary artery

·         LAD – septal branch

Posterior V7, V8, V9 V1, V2, V3 Right coronary or circumflex artery
Right ventricle V1R-V6R I, aVL Right coronary artery

·         Proximal branches

Other interesting/useful resources:

Academic Day Seminar – Feb 10 (Osteomyelitis)

✔ Osteomyelitis

Condition: Infection localized to the bone

Classifications:

  • Hematogenous: bloodstream (mono-microbial) – 19%
    • more common in children (metaphysis of skeletally immature patients → bone plates are still growing and requiring abundant blood supply)
    • in adults, vetebra most common site (lot of blood supply which is also “sluggish” in this location)
  • Contiguous: adjacent soft tissue infection gains access to bone (polymicrobial) – 47%
    • younger individuals with trauma, open fx, surgery
    • older adults secondary to decubitus ulcers & infected total joint arthroplasties
    • Can affect any bone; RF: fractures, surgery, prostheses
  • Peripheral vascular disease – 34%
    • Diabetes
  • Acute: < 2 weeks
    • Introduction of microbes into bone → tissue necrosis
    • Difficult for host inflammatory cells and abs to reach necrotic area
  • Subacute (2-4 weeks)
  • Chronic: >4 weeks or relapse
    • Appearance of dead bone, fistulous tracts

Pathogens:

  • Hematogenous: mono-microbial, S. aureus
    • IVDU: G(-)s: Pseudomonas (80%)
      • Pseudomonas lives ins most water/soil – so if use dirty water for IVDU, would increase risk of Pseudomonas
    • >50 y/o: tend to see more G-s (e.g. E coli) d/t more UTIs in this pt pop
  • Vertebral:
    • Lumbar + Thoracic
    • S. aureus 60%
    • E. coli
    • Mycobacterium tuberculosis
  • Sickle cell anemia:
    • Salmonella 66%
    • Bowel infarction facilitate salmonellae bacteremia
  • Contiguous
    • Polymicrobial or monomicrobial
    • S. aureus most common
    • S. epidermidis, P. aeruginosa, E. coli, Proteus, Strep, anaerobes
  • Vascular insufficiency
    • Polymicrobial
    • Staph, Strep, Enterobactericiae, Enterococcus, Bacteriodes, anaerobes
    • RF: pressure sores, DM, PVD; Often bone in feet involved
Diagnostics Clinical Presentation
  • Probe to bone
  • Imaging:
    • Xrays (bone changes not seen until 14 ds)
    • MRI: preferred; sensitive as early as 3-5 ds (observes infection presence and extent, distinguishe between soft tissue and bone infection)
    • CT scan: modaility of choice if no MRI (not as sensitive or specific as MRI)
    • Bone scan: accumulates in osteoblastic activity (therefore distinguish OM from cellulitis; low sensitivity, esp with recent trauma or surgery)
    • Gallium scan: affinity to acute phase reactants + areas of inflammation; may combine with bone scan
    • WBC scan: sites of inflammation or infection;
      Combining with bone scan can increase specificty
  • Lab:
    CRP, ESR
  • CXs
    – Bone aspiration/biopsy
    – intra-op tissue cx
    – BCx
    – Open wounds and draining sinuses contaminated
CNS: +/- Fever
MSK: Localized bone pain/tenderness, warmth, decreased limb motion
DERM: redness, edema in affected area
Labs: WBCs, ESR, CRP may increase
ID: BCx + in 50% with hematogenous OM. Perform bone aspiration, biopsy, bone Cx

  • Hematogenous:
    – pain, tenderness, warmth, erythema, swelling, reduced range of motion, fever, chills, malaise
    – vertebral OM: severe dull back pain, may have systemic symptoms
  • Contiguous:
    – localized pain, tenderness, warmth, edema, erythema
    – post-surgical: sxs manifest within 1 mos as pain
  • vascular insufficiency
    – pain, erythema, redness
    – bone exposed assume

Complications

  • Local bone damage, necrosis
  • apposition of new bone
  • recurrence
  • sepsis
  • mortality

GoTs:

  • Treat the infection
  • Restore bone and joint function
  • Prevent progression to chronic OM
    • Chronic → poorer prognosis as necrotic bone acts as bacterial reservoir and inability to remove all dead bone may require suppressive therapy
  • Prevent recurrence
  • Minimize ADRs

Treatment

  • Starting empirically:
    • For stable patients or those with stable OM: when cxs are obtained during debridement or bone biopsy
    • For septic, hemodynamically unstable or have neurological compromise: right away
  • Modify therapy based on micro
  • Treat for 4-6 weeks – consider treating for 8 weeks if drug-resistant e.g. MRSA

Concepts

  • Go HIGH (but relationshiop b/w dose and concentration in bone and therapy outcome unknown) and Go IV
  • Good penetration: B-lactam, cephalosporin, clindamycin, fluoroquinolones, septra, doxycyline, metronidazole
    • But…NOT oral B-lactams
    • Metronidazole dosed Q8H not Q12H
  • When to step down → afebrile, clinically stable and improving, can tolerate PO intake, adherent medicallys
    • Not neonates or immunocompromised
    • Generally in 2 weeks (based on small retrospective study)
  • SOURCE CONTROL: debridement, removal or hardware, revascularization
    gnerally considered for: chronic OM, DFI, worsening infection despite antimirobial tx

✔ Prosthetic Joint Infection

Condition: Infection of joint replacements (can occur after total hip arthroplasty, or total knee rthroplasty) → Can lead to loss of joint function and structure, mobility, risk of sepsis, mortality

Pathophysiology: prosthesis allow for biofilm to develop → biofilm protects microbes from host → as biofilm develops, microbes less susceptible to antimicrobials

Common organisms:

Onset Microbes introduced Common organisms
Early (within 3 months) At time of surgery Staph aureus, GNB, anaerobes
Delayed (3-12 months) At time of surgery CoNS Staph, Enterococci
Late (>12 months) Hematogenous source Staph aureus, beta-hemolytic streptococci, GNB

Assessment:

  • Symptoms: acute onset or chronic pain unresolved by joint replacement
  • Persistent wound drainage around prosthesis
  • ESR and CRP may increase
  • Imaging tests: X-ray
  • Gram stain: only 1/3 positive (low sensitivity)
  • Joint culture: highly sensitive and specific
  • Joint fluid analysis: Increased WBCs and neutrophils, purulence

Treatment

  • Source control: debridement and prosthesis retention, prosthesis removal, amputation, resection arthroplasty
  • Duration of abx: 4-6 weeks, except for Staphylococci – treat for 2-6 weeks with IV abx (+ rifampin PO 300mg BID) then switch to PO abx (+ rifampin PO 300mg bid) for total 3-6 months (6 mos if receiving TKA)
    • Rifampin can penetrate into biofim, has synergistic activity in combintion with other antimicrobials …but NOT to be given as monotherapy or before surgical intervention due to risk of rapid resistance development in presence of high bacterial inoculum size

Academic Day Seminar – Feb 10 (Endocarditis)

Great job by Merisa and May! This was an excellent and well-organized presentation on different infectious diseases. 🙂

It was also great to have Dr. Lau provide us with clinical pearls, as well as, remind us to think about:

  • How to explain the infection and diagnostics in a patient-friendly manner
  • How to “make sense” of the clinical findings and recommended treatment (rather than trying to memorize)

✔ Endocarditis

Condition: Infective endocarditis is inflammation and infection of the inner lining of the heart (endocardium), which can affect the valves.
→ Surface of heart valve is damaged leading to formation of a clot on the valve (valves have tiny blood vessels nourishing them)
→ When bacteria is introduced to the blood, it clonizes and sticks to clot
(Strep + Staph produces dextran to help them stick to valves, G- don’t produce dextran and are less likely to stick)
→ Formation of “vegetation” of fibrin, platelets and bacteria protects the bacteria from the host

Complications:

  • Local valvular damage → HF, valvular insufficiency
  • Septic emboli → stroke, hemorrhage, pulmonary emboli, mycotic aneurysms, spleen infarction/abscess, kidney infarction, glumerulonephritis, petechiae, Janeway lesions, Osler nodes
  • 4-50% risk of mortality depends on organisms involved

Signs and symptoms: usually non-specific symptoms when presenting acutely – if see physical findings on skin, sign that it is long-term endocarditis and prognosis is not good

CNS Fever (most common), chills, weakness, malaise, sweats, stroke, delirium/coma, cerebral emboli, headache
HEENT Roth spots (2-10%), retinal hemorrhages (not specific to IE), soft palate petechiae, conjunctival petechiae
RESP Dyspnea, cough, hemoptysis, pulmonary emboli è Associated more with R sided endocarditis
CVS New or changing heart murmur (85%), chest pain, CHF
GI Splenomegaly, anorexia/weight loss, N/V, abdominal pain
GU Renal failure (↑sCr), proteinuria, hematuria
è Associated more with L sided endocarditis as blood flow is going to periphery
Heme ↑ WBC/neutrophils, ↓Hgb, ↓PLT, ↑ESR, ↑ CRP, bacteremia (90-95%)
Skin
/MSK
Petechaie (small red/purple spot due to bleeding into skin on skin extremities or on mucous membranes), Splinter hemorrhage, Janeway lesions, Osler nodes, clubbing, myalgia/arthralgia, back pain

Diagnostics: clinical, laboratory + echocardiographic findings

  • Modified Duke Criteria: developed for evaluation of L sided native valve
    → sensitivity (ability to r/o dx) is diminished in prosthetic valve IE, R sided IE and cardiac device infection
  • TTE, TEE
    → similar specificity, but TEE is more sensitive in detecing abscess and vegetation
    → TTE also lacks sensitivity in assessing valves
  • Snout → Sensitivity → negative = rule out
  • Spin → Specificity → positive = rule in
  • Negative result does not exclude infection as vegetation may be small or have embolized
  • Consider how to explain diagnostics to patients
    For example:
    (1) TTE has a sensitivity of  58-63% → meaning that if patient does have endocarditis, we could detect it 58-63% of the time (so not good for diagnosis, but good for screening since relatively high specificity)
    → if high sensitivity, if the test is negative – we can rule out diagnosis
    → if low sensitivity = increased rate of false –
    (2) TEE/TEE has a specificity of ~90% → meaning that if patient does not have endocarditis, ~10% of the time it will be a false +
    → if high specificity, if the test is positive → we can rule in diagnosis
    → if low specificity, increased rate of false +

    • Would do TTE first and if negative but still suspect endocarditis, would do a TEE

Epidemiology:

  • More common in > 50 yo (younger in IVDU)
  • More common in males (Male:Female ratio 2:1)

Risk Factors: → Essentially conditions that affect blood flow

  • Host → Heart disease
    • Valvular: Prosthetic valve(s), Degenerative valve disease, Rheumatic heart disease (may be precipitated by Strep Throat) → damage of heart valves, Mitral valve disease, Aortic valve disease
    • Congenital: Patent ductus arteriosus, Ventricular septal defect, Tetralogy of Fallot, Coarctation of aorta
    • Structural – Hypertrophic cardiomyopathy
  • Poor Immune System
  • Previous IE
  • Ask yourself: Where is the bug coming from? 
    → Cardiac implantable devices
    → Poor dental hygiene
    → Hx of IV drug abuse (IVDU usually affects tricuspid valve)
    → Prolonged indwelling line access
    → Long term HD

Pathogens:

  • Staph + Strep: 80% of cases
  • Enterococcus sp.
  • HACEK group organisms
  • Culture negative (usually due to prior antibiotics)

Treatment:

  • High doses of parenteral bactericidal antibiotics for an extended duration
  • Duration counts from 1st day of negative BCx in cases where initial BCx was +

STAPHYLOCOCCUS AUREUS
→ high virulence + common in IVDU and patients with intravascular catheters
→ associated with higher rates of embolism and mortality (25-47%) compared to other organisms (exception: R sided S. aureus IE in IVDU) 

I. MSSA in Native Valve

  • L sided:
    Cloxacillin 2g IV Q4H x 6 weeks + Gent 1mg/kg IV/IM Q8H x 3-5 ds
  • R sided, complicated (metastatic infection, renal failure, abscess formation, HIV, vegetation >1-2 cm):
    Cloxacillin 2g IV Q4H x 6 weeks + Gent 1mg/kg IV/IM Q8H x 3-5 ds
  • R sided, uncomplicated:
    Cloxacillin 2g IV Q4H + Gentamicin 1mg/kg IV/IM Q8H x 2 weeks
    → but in practice, commonly more aggressive and tx x 6 weeks
  • IDSA guidelines recommend against gentamicin for MSSA
    • Addition of AG may more rapidly clear bacteria from blood by ~ 1 day but no difference in survival
    • Risks (increased nephrotoxicity, monitoring) vs. Benefits
    • In practice, tend not to add AG unless bacteremia is persistent >7ds
  • If non-anaphylaxis B-lactam allergy: replace clox with cefazolin 2g IV Q8H
  • If anaphylaxis B-lactam allergy: replace clox with vancomycin (vancomycin kills more slowly than cloxacillin)
    • Other option is high dose daptomycin 8-12mg/kg (by expert opinion) – concentration-dependent antibiotic

Why shorter duration for R sided vegetations?:
Good prognosis + Clinical and microbiologic cure > 85%
IDSA 2015: Right-sided vegetations tend to have lower bacterial densities, which may result from host defense mechanisms, including polymorphonuclear activity or platelet derived antibacterial cationic peptides

II. MRSA in Native Valves

  • L sided or R-sided:
    Vancomycin 15mg/kg IV Q12H x 6 weeks + Gent 1mg/kg IV/IM Q8H x 3-5ds
  • IDSA recommends use of gentamicin for tx of NVE caused by MRSA

*PROSTHETIC VALVE = 3 AGENTS d/t high mortality rate with S. aureus PVE

  • Rifampin is added for biofilm penetration (some studies show that may develop resistance if add while still bacteremic)…but in practice, some would start rifampin with other therapy
  • May need valve replacement

III. Prosthetic Valve MSSA

  • Cloxacillin 2g IV Q4H + Rifampin 300mg PO/IV TID > 6 weeks
    + Gentamicin 1mg/kg IV/IM Q8H x 2 weeks

    • Rifampin IV is special access, but PO has good oral bioavailability

IV. Prosthetic Valve + MRSA

  • Vancomycin 15mg/kg IV Q12H + Rifampin 300mg PO/IV TID > 6 weeks
    + Gentamicin 1mg/kg IV/IM Q8H x 2 weeks

STAPHYLOCOCCUS EPIDERMIS (CoNS) → health care associated

  • Loves to stick to prosthetic valves
  • Entry: valve surgery, infected IV catheter (health care-associated)
  • Most common in early (
  • Typically methicillin-RESISTANT
  • Will likely require valve replacement

Treatment:

I. Native Valve: empirically as per MRSA regimen for NVE

  • Vancomycin 15mg/kg IV Q12H x 6 weeks + Gent 1mg/kg IV/IM Q8H x 3-5ds

II. Prosthetic Valve: empirically as per MRSA regimen for PVE

  • Vancomycing 15mg/kg IV Q12H + Rifampin 300mg PO/IV TID x > 6 weeks
    + Gentamicin 1mg/kg IV/IM Q8H x 2 weeks

STREPTOCOCCUS 

  • Most are Viridans Streptococci (source: human mouths)
  • Tx is also the same for Streptococcus bovis (source: gut) – not a viridans strep
  • Mortality rate (4-16%) is lower than S. aureus
  • Low virulence, typically easier to treatment
  • *REQUIRE MIC of PENCILLIN*

I. Highly Penicillin-susceptible Streptococcus (MIC < 0.12)
a. NVE (uncomplicated, normal renal function)

  • Pen G 12-18MU/d IV continuously or in 4-6 divided doses or CTX 2g IV/IM Q24H
    + Gent 1mg/kg IV/IM Q8H or 3mg/kg IV/IM daily x 2 wks

b. NVE (complicated – >65 yo, impaired eight cranial nerve function, abscess, poor renal fx)

  • Pen G 12-18 mU/day IV or CTX x 4 weeks
    • easier to treat so 12-18 instead of 24 (SPH has PPO guiding to 12-18 dosing, but VGH will do 24mU/day IV)

c. PVE

  • Pen G 24mU/day IV or CTX x 6 weeks
    + Gentamicin.x 2 weeks (tend not to add gentamicin but can add if concerned)

II. Relatively Penicillin-Resistant Streptococcus (MIC > 0.12mg/L to < 0.5mg/L)
→ IDSA recommends ID consult

a. NVE

  •  Pen G 24 mU/day IV or CTX  (or Vanco if B-lactam allergy) x 4 weeks
    + Gent 1mg/kg IV/IM Q8H or 3mg/kg IV/IM OD x 2 weeks

b. PVE

  • Pen G 24 mU/day IV or CTX (or Vanco if B-lactam allergy) x 6 weeks
    + Gent 1mg/kg IV/IM Q8H or 3mg/kg IV/IM OD x 6 weeks

III. Highly Penicillin-Resistant Strep (MIC > 0.5mg/L) → IDSA recommends ID consult

  • Generally go with vancomycin and not depend on penicillins
  • Typically treat as enterococcal IE
  • If pen-resistant, usually also amp-resistant as quite similar for Strep coverage

a. NVE

  • Pen G 18-30 MU/day IV or Amp 2g IV Q4H or Vanco IV + Gent 1mg/kg IV/IM Q8H
    →Duration as per ID

b. PVE

  • Pen G 24 mU/day IV or CTX or Vanco + Gent 1mg/kg IV/IM Q8H or 3mg/kg IV/IM OD
    → Duration as per ID

For Abiotrophia defectiva and Granulicatella species (nutritionally variant strep) are typically difficult to grow and treat → Would always recommend PEN + AG (but practice may differ)

ENTEROCOCCUS

  • Source: Gi tract (occasionally anterior urethra)
  • Low virulence but can be pathogenic in predisposed pts following GU procedures
  • More commonly E. faecalis (90% of isolates) and can also be E. faecium
  • More difficult to treat than staphylococci and streptococci because…High MIC to penicillin, Intrinsic resistance to all cephs and relative resistance occurs to AMG (low level of AMG resistance), increasing resistance and need combination of cell wall active agent AND AMG for killing

Susceptibilities:

  • (S) Pen, Amp, Gent, Strep
    → Pen G 18-30 MUéday IV or Amp 2g IV Q4H + Gent 1mg/kg IV/IM Q8H x 4-6 weeks
    (NVE: 4 weeks if symptoms of illness ❤ mos, 6 weeks if symptoms >3 mos)
    (PVE: 6 weeks)
    OR
    → Amp 2g IV Q4H + CTX 2g IV Q12H x 6 weeks

    • Why is CTX an option? Amp binds to PBP which impairs cell wall synthesis…but it doesn’t bind to all types of PBP so the cell wall can still repair itself. CTX will bind to the other types so that it cannot rebuild itself
  • (S) Pen, Amp, Strep BUT…(R) Gent
    → Pen G 18-30 MU/day IV or Amp 2g IV Q4H x 4-6 weeks
    + Streptomycin 7.5mg/kg IV/IM Q12H (→ usually 500mg IV Q12H, drop to 250mg IV Q12H if reduced renal function) x 4-6 weeks
    (NVE: 4 weeks if symptoms of illness ❤ mos, 6 weeks if symptoms >3 mos)
    (PVE: 6 weeks)
  • (S) Pen, Amp BUT…(R) Strep, Gent
    → Amp 2g IV Q4H + CTX 2g IV Q12H x 6 weeks
  • (S) Gent, Strep BUT…(R) Pen, Amp
    → Vanco IV + Gent 1mg/kg IV/IM Q8H x 6 weeks
  • (R) Pen, Amp, Gent, Strep
    → Vanco IV x 6 weeks
  • (R) Pen, Amp, Gent, Strep, Vancomycin
    → Linezolid 600mg IV or PO Q12H x > 6 weeks
    OR
    → Daptomycin 10-12mg/kg/day x > 6 weeks
    Based on limited case studies → involve ID, cardiology, CV surgery and clinical pharmacist

HACEK
Haemophilus, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens, Kingella sp

  • Accounts for ~5-10% of community acquired NVE in non-IVDUs
  • Grows slowly in blood cx media. Failutre of growth in in-vitro susceptibility testing is common
  • Previously susceptible to ampicillin, but growing resistance due to B-lactamase producing strain

NVE and PE

  • PREFERRED CHOICE:
    CTX 2g IV/IM Q24H or cefotaxime 2g IV Q8H x 4 weeks for NVE or 6 weeks for PVE
    OR
  • Amp 2g IV Q4H x 4 weeks (ONLY if C+S shows sensitivity as growing resistance)
    OR
  • Cipro 500mg PO Q12H or  400mg IV Q12H
    • only bsaed on a few cases reports…may be considered if patient cannot tolerate CTX

Culture-negative endocarditis:

  • Consider: previous ab use before blood cx, inadequate microbiological techniques, infection with highly fastidious bacteria or fungi, noncultivatable agents
  • Fungi → valve surgery for most cases
  • Brucella → usually requires valve replacement
  • Bartonella (RF: alcoholism, homelessness, contact with cats ㅇㅅㅇ)
    → Doxycyline + AMG
    → Will likely need valvular surgery
  • Q fever (bacteria spread by aerosol transmission by animals)
    → Hydroxychloroquine + Doxycyline x 18-24 months
    → 
    Will likely require surgical valve replacement

Non-pharmacological therapy

  • Surgical indications:
    • determined by cardiologist, ID, surgeon
    • Fungi IE
    • complication of HF, heart block, destructive penetrating lesions
    • failure of abs: persistent bacteremia or fever lasting >5-7 ds after the start of appropriate abs, or recurrent emboli or enlarging vegetation despite appropriate abs
    • severe valve regurgitation and mobile vegetations >10mm

Monitoring:

  • BCx → usually see bacteremia x 3 -7ds (not a sign of tx failure, but an expected course for endocarditis)…if BCx clears 1-2 days after, unlikely to be endocarditis!
    • After obtaining a negative BCx, wouldn’t repeat unless clinically deteriorating
    • repeat 2 sets of BCx Q24-48H until blood stream infection has cleared
  • Gentamicin levels: 1 hr after a 30 min infusion: 3mg/L, trough <1mg/L
    • baseline audiometry – test for high and low frequency, and e-test for vestibular toxicity then q weekly
  • Vancomycin trough levels: 15-20mg/L
  • CNS: resolving fever within ~ 5ds
  • CVS: repeat TTE at abx completion → not generally done in practice to assess valvular damage

Other clinical pearls:

  • ESR is elevated as erythrocytes are binding to inflammatory proteins and sedimenting at a faster rate
  • Renal adjustment for penicillins: B-lactam is time-dependent → would adjust dose (instead of interval); therefore, for Pen G 4mU IV Q4H should ideally be adjusted to 3mU IV Q4H for aggressive infection
  • Renal adjustment for aminoglycosides or fluoroquinolones → would adjust interval
    E.g. cipro 400mg IV Q12H → 400mg IV Q24H

Resources:

Other types of endocarditis:

  • Non-bacterial thrombotic IE: also known as  marantic endocarditis
    • Non-infectious endocarditis, characterized by deposition of sterile platelet thrombi on heart valves (mostly aortic and mitral)
    • Causes:
      • Most commonly associated with advanced malignancy
      • Other etiologies: SLE, inflammatory conditions (e.g. antiphospholipid syndrome, rheumatic heart disease, rheumatoid arthritis, sepsis, burns)
      • Thought that hypercoagulable state is critical in development
    • Manifestations:
      • often asymptomatic..clinical manifestations result from systemic emboli (e.g. to spleen, kidney, skin and exremities)
    • Treatment:
      • Anticoagulation and therapy directed at treating the underlying malignancy or associated condition
      • Hematology consult…typically indefinite anticoagulation
      • Uptodate: therapeutic LMWH or IV UFH

 

Academic Day Seminar – Jan 27

✔ Diabetes

Andrea and Rinche did a great job covering diabetes! Despite seeing a lot of insulin sliding scale orders, I have yet to see a BNC insulin regimen and am glad that the session covered this in depth! 🙂

Some ways I will apply this session:

  • Explain “diabetes” in patient-friendly terms
    • T1DM: cannot make insulin
    • T2DM: unable to respond to insulin (insulin resistance) or unable to make enough insulin in response to high blood sugars (abnormalities in insulin action)
  • Clinical Pearls with Insulin:
    • If glargine or detemir is used, the dose adjustment should be based on the morning fasting blood glucose level
    • If NPH is used, the dose adjustment should be based on the morning fasting blood glucose level or the blood glucose level measured before the evening meal
    • If bolus insulin is used, dose adjustment should be based on the next reading
      → Morning insulin – pre-lunch BG
      → Lunch insulin – pre-dinner BG
      → Dinner insulin – HS BG
    • If previously insulin naive, patients who require >10 units/day of insulin in hospital will likely require insulin after discharge
      • Consider NPH 10 units QHS and GP f/u and consult diabetes specialists (RN education/clinic/endocrinologist)
    • Contraindicated/not recommended combinations:
      • Insulin + Linagliptin → possible increase in CV risk
        (not a class effect for DPP-4 inhibitors; relatively low risk of hypoglycemia with DPP-4 inhibitors on its own)
      • Insulin + Pioglitazone → increase risk of fluid retention
      • Insulin + SU → increase risk of hypoglycemia
      • Dapagliflozin + Pioglitazone → individual use in bladder cancer active or hx is contraindicated – therefore, combo in general is not recommended
      • Pioglitazone + MTF + SU → increase risk of fluid retention
  • In-hospital management of non-ICU patients:
    scheduled Basal, Nutritional, Correctional SC insulin → prevents reactively responding to high BS

    • GoTs: use as little correctional insulin as possible + provide most of insulin as regularly scheduled basal and nutrition insulin
    • *Remember to consider patient’s PO intake…any outside food?
    • CDA targets: Non-ICU Pre-prandial: 5-8, Random < 10 mmol/L
    • Evidence:
      1. RABBIT-2 ISS vs. BNC in medical pts
      → BNC resulted in significant improvement in glycemic control but no difference in hypoglycemia or length of hospital stay
      (no clinical efficacy outcomes)
      2. RABBIT-2 Surgery ISS vs. BNC in surgery pts
      → less post-op complications (e.g. wound infection, pneumonia, renal failure, bacteremia, respiratory failure – ?which was driving this), no difference in severe hypoglycemia (<2.2) or length of hospital stay…BUT more hypoglycemia in BNC arm
      3. VGH Post-BNC PPO vs. Pre-BNC PPO
      → BNC PPO resulted in lower BG and less severe hyperglycemia (>12), no difference in hypoglycemia (<4)
  • Clinical Pearls for Special populations:
    • Heart Failure
      • Pioglitazone + Rosglitazone are contraindicated for HF in Canada
        → cause fluid retention
      • Linagliptin, sitagliptin use not recommended; saxagliptin (1 HF hospitalization for every 143 patients over 2 yrs) caution warranted; alogliptin caution in NYHA III and IV
        → mechanism unknown
      • Empagliflozin may be of benefit to reduce HF-related hospitalizations (EMPA-REG)
    • Renal impairment
      • Linagliptin does not have to be renally adjusted until eGFR <15
        • When eGFR < 15, caution and/or reduce dose
        • + it is formulary in hospital
      • Metformin is contraindicated if eGFR < 30mL/min; when eGFR 30-45, do not initiate and reduce dose by 50% according to Lexicomp
        • CDA guidelines more conservative and states caution and/or reduce dose when eGFR 30-60
        • intravascular iodinated contrast agents possibly increase risk of lactic acidosis
      • Out of the SUs, safest for renal impairment is gliclazide which is contraindicated when eGFR <15, with caution and/or reduce dose when eGFR 15-30 AND has a lower risk of hypoglycemia than glyburide
        • However…gliclazide = limited coverage vs. glyburide = regular benefit 😦
      • Acarbose – not recommended when eGFR < 25 mL/min
      • Dulaglutide: once weekly and no renal or hepatic impairment adjustment
        • New GLP-1 agonist
  • Sick Day Meds List: SADDMANS
    Sulfonylurea, ACEIs, Diuretics, Direct renin inhibitors, Metformin, ARB, NSAIDs, SGLT-2 inhibitors

    • If hypoglycemic (BG < 4 mmol/L), give 15-20g of carbohydrates (e.g. 4-5 dextrose tablets/2 containers of apple juice/2-3 packages of honey)
      → Rpt BG in 15 mins, if <4 mmol/L, give another 15-20g of carbohydrates and Rpt BG in 15 mins, if persistently <4 mmol/L contact MD
    • After initial glucose treatment, another carbohydrate containing snack should be taken within 1 hour. If meal more than 1 hour away, a snack with 15g carbohydrate & protein source is also recommended
      • sucrose will not be absorbed with acarbose (give dextrose or honey)
  • CV trials for new diabetic medications:
    • In order for approval by Health Canada – it needs to demonstrate CV safety (i.e. no increased CV risk vs placebo as part of standard care) by non-inferiority

Resources:

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