This session for me was an excellent reminder of what was covered during undergrad, with additional information on management of A-fib in the emergency department – it also was great to review my V-W antiarrhythmic classes. Actually, it made me think of my Toxicology rotation. Certain classes of antiarrhythmics influence certain ion channels in myocytes, which may affect the ECG. I thought back to certain toxicities – sodium channel = prolonged QRS complex, which potassium channel = prolonged QTc interval.
What I found really valuable from this presentation were actually the series of flashcard-like slides, which were a good reminder of the ADRs associated with each of the medications used for rhythm control (flecainide, amiodarone, dronedarone, sotalol). I hope to apply what I learned during this ADS to my upcoming Emergency rotation.
I think the bottom line for this ADS is “Adam, you need to review your primary literature for anticoagulation”. The session certainly brought up a lot of primary literature, but also raised a couple of clinical controversies. The take-home messages I got were:
– Basically anyone who is immobile, has recently had surgery, or has cancer or another medical condition predisposing to clots requires DVT prophylaxis. Harking back to Clinical Orientation, the words of Mike: “You need to talk yourself out of DVT prophylaxis rather than into DVT prophylaxis”.
– Hip surgery > knee surgery for clot risk, therefore treat longer.
– The BRIDGE trial only included A-fib patients with a mean CHADS2 of 2, so only consider bridging therapy for high-risk clotters…in terms of other high-risk clotting scenarios, there is less to no evidence.
– CONTROVERSY: the rivaroxaban EINSTEIN-PE trial, although it showed non-inferiority to warfarin, had a wide confidence interval (CI), whereas AMPLIFY had a tighter CI when showing non-inferiority to warfarin.
– I always thought VTE treatment in cancer patients was always with indefinite duration until malignancy is resolved, but it turns out it is >6 months. PO options for this population are pending trials (MATISSE subgroup)
I always felt from undergrad that electrolytes as a topic was some sort of nebulous concept… your patient has low potassium, so what are you gonna do? Replace it of course! Also, in the renal elective we got a run-down of hypo and hyperkalemia, derangements in acid/base balance (including anion and non-anion gap acidosis), but this ADS dove a bit deeper into how all those parameters interplay with each other. Some take-home messages I got:
– Digoxin and electrolyte balance are quite closely interrelated. Basically you need extracellular potassium to work the pump, and you need magnesium as a cofactor for the pump. Digoxin binds to that pump. Less K = more dig can bind = less Na-K pump activity.
– Low Mg can result in low K, Na, PO4, and low Ca. In other words – no matter what you do, replace the magnesium along with the others.
– I finally learned what “refeeding syndrome” actually means. I encountered a couple of cases on my Oncology rotation, but never grasped the mechanism behind it. Basically if you are in a ketogenic state and making your carbs from ketones and free fatty acid breakdown (>72 hrs after your last bite of food), if you aggressively refeed the patient, glycolysis intermediates contain phosphorylated compounds, which need phosphate —> high demand = low PO4.
I also enjoyed the cases, as they allowed us to put everything together. I can now appreciate the importance of the magnesium, and can confidently recommend replenishment strategies (after memorizing a couple of products and doses!)
Upper GI bleeds (UGIB) – I always thought that the colour of the stool is a good indicator of whether it is an UGIB or lower GIB (LGIB). However, I learned that it wasn’t a sensitive indicator, although it can aid in the diagnosis. General management for a non-variceal bleed is as follows:
– IV PPI (increases gastric pH –> stabilizes blood clots –> improves survival). Is intermittent dosing better, or continuous infusion better? This meta-analysis seems to say that there is a 28% RRR (2.64% ARR) for re-bleed within 7 days for intermittent dosing, although the results were pooled from a variety of intermittent regimens.
– Prokinetics: only warranted if endoscopy is needed to rule in or rule out UGIB. Erythromycin 3 mg/kg IV over 20-30 mins, 30-90 mins pre-procedure.
– Somatostatin and octreotide: clinical efficacy proven, but PPIs and prokinetics (with endoscopy) are much cheaper and there is more clinical experience.
Splenic infarcts and abscesses: when are antibiotics indicated?
Splenic INFARCTS: due to a whole bunch of different diseases, such as underlying cancer, embolic disease (such as A-fib or IE), splenomegaly, trauma. Treat the underlying cause.
Splenic ABSCESS: usually results from an endocarditis. May be accompanied by left-sided pleural effusion. This requires drainage + antibiotics +/- splenectomy. Usually the abscess is polymicrobial – usually E coli, Streptococcus spp, Enterococcus spp, and anaerobes.
This was a highly enjoyable session conducted by Dr. Loewen. His one-pager outlines the process one may follow when assessing fluids. Although it is a non-traditional activity for a pharmacist to order IV fluids for resuscitation purposes, and it would be difficult to incorporate this into a daily workflow if one is a clinical pharmacist covering 40-50 beds…it is still good to keep this in mind if only to reassess orders that have been written. I will apply myself to learn how to do a JVP and perform a volume assessment if someone has not done it already…and now I know where various IV crystalloids end up!
The main thing I wanted to know was discussed – screening for drug-caused SIADH. Euvolemic hyponatremia is the main filter, as if a patient presents with that, the list of things that can cause SIADH is quite extensive, which include CNS or respiratory insults – i.e. pneumonias. Hopefully I come across a case of euvolemic hyponatremia so I can put this to practice!
We meet again, University of Kentucky Clinical Pharmacokinetics Manual…although phenytoin and digoxin are two drugs which are not used that often (phenytoin definitely not used as often as it was before), it’s two tools that would be helpful in a clinical pharmacist’s arsenal in order to deliver timely, effective and safe pharmacotherapeutic care. The following is what I gathered from the session in order to deliver EFFICIENT and SAFE care (not necessarily perfectly calculating every patient’s individual PK parameters). I look forward to tackling some phenytoin and digoxin PK conundrums on my rotations!
Phenytoin – the skinny on how it is dosed and adjusted – my flowchart
Remember: mg/L * 4 = umol/L
1) Is the patient actively seizing?
YES – load immediately with 15-20 mg/kg IV phenytoin, max rate 50 mg/minute. You don’t have time to calculate a load! Take a level two hours after giving the dose. If the patient is actively seizing while on phenytoin, may give diazepam to abort the seizure.
NO – may load empirically with 13-15 mg/kg PO/IV phenytoin depending on whether they are post-ictal, and start a maintenance dose 8-12 hours after depending on what trough you are aiming for. For PO, take a level 24 hours after giving for a peak.
2) What maintenance dose do I give?
EMPIRICALLY – 5-7 mg/kg
THE LONG WAY (use only if you are unable to achieve adequate troughs with multiple attempts) – look up the patient’s Km (more likely to be stable), calculate the Vm given the Css and dose you have. Back-calculate the necessary dose given the Vm you just calculated.
3) My patient is hypoalbuminemic – what do I do?
ESRD – observed phenytoin/(albumin*0.02 + 0.1) = corrected phenytoin
NO ESRD – observed phenytoin/(albumin*0.01 + 0.1) = corrected phenytoin
4) Do I need to give a mini-load?
IT DEPENDS – on if the patient is near the top of their 5-7 mg/kg empiric range, if they recently seized, if they are experiencing phenytoin-specific toxicity, i.e. drowsiness is NOT a specific symptom
5) My patient is exhibiting phenytoin toxicity and has trough levels exceeding 80 umol/L – how long do I wait for the level to drop below 80?
RULE OF THUMB – 1 day, for every 20 umol/L over 80. Exceptions are if the patient is extremely supratherapeutic (>>120 umol/L), in which case order daily phenytoin levels.
6) At which serum levels would I expect to see certain toxicities?
>120 umol/L = nystagmus and ataxia
>160 umol/L = altered mentation
>200 umol/L = coma.
Digoxin – the skinny on how it is dosed and adjusted – my flowchart
1) How do I load a patient on digoxin? (not really recommended in heart failure…)
EMPIRICALLY – 8-12 mcg/kg IV of LEAN (ideal) body weight
THE LONG WAY – Vd = 7 L/kg, C = 0.6-1 ng/mL for HF, 1.2-1.5 ng/mL for A-fib, F = 0.7 for tablets, S = 1. Calculate PO dose = (Vd * C)/(SF).
REGARDLESS OF HOW YOU CALCULATE, load 1/2 the dose stat, then 1/4 x 2 doses Q6H.
2) When and how much do I give digoxin for maintenance?
0.125-0.25 mg PO daily, or 2.4-3.6 mcg/kg IV daily.
3) Do I need digoxin levels? – no. Do them if and only if you suspect toxicity.
4) How do I give Digibind? – https://lifeinthefastlane.com/ccc/digibind/, may need to repeat dosing later due to extensive distribution and high volume of distribution. Take repeat levels to assess response.
Another gem for digoxin toxicity from one of my favourite blogs, which I am sure will come in handy for Emerg rotation – https://lifeinthefastlane.com/ccc/digoxin-toxicity/
Two of our fellow residents delivered a very helpful seminar on the diagnosis, presentation, and treatment of HFrEF (more emphasis on this) and HFpEF. For me, it was a helpful reminder of the landmark trials, as well as a great therapeutic update on the recent SHIFT and PARADIGM-HF trials for ivabradine and sacubitril/valsartan, respectively. Here are some of the take-home messages I got:
– A useful way to assess orthopnea is to ask the patient how many pillows they use at home to achieve adequate comfort while breathing
– Triple (ACEI/ARB + BB + MRA) therapy to target doses plus loop diuretic titrated to benefit is still the backbone of HFrEF pharmacotherapy
– The only reason furosemide does not have a RCT demonstrating mortality benefit is that it would be unethical to withhold loop diuretics from HF patients
– CLINICAL PEARL: for renal impairment, effective dose of furosemide may be estimated by calculating SCr divided by 2!
– HFpEF therapy = treat the comorbids and risk factors for HF in general (i.e. smoking, HTN, COPD, liver and renal disease…)
– Hydralazine and ISDN, together, are thought to mimic ACEI action – may be more beneficial in patients of African-American descent
– Ivabradine is kind of like a new digoxin in terms of its effects on heart rate and its morbidity but no mortality benefit, but it only has chronotropic effects
– Anecdotal evidence quips that many patients cannot tolerate the doses of sacubitril/valsartan that was used in the trial (200 mg PO BID)
I’m confident I will encounter numerous HF patients during my various rotations, so I’m glad that this ADS came up relatively early so that I can be more efficient in identifying DTPs – already on clinical orientation and my 4th year hospital rotation I came across two patients who had NEVER been tried on ACEI or ARB for their HFrEF despite not having any absolute or relative contraindications…these patients would certainly benefit from intervention!
I notice that quite a few of the patients I have encountered so far in Clinical Orientation and my 1st patient on my Oncology rotation are on SMX/TMP for PCP prophylaxis. It begged the question: when is it warranted? According to this meta-analysis, if the risk is >6%, you give prophylaxis. Which conditions warrant this type of risk? Should all cancer patients receive it?
– Cancer patients who SHOULD receive PCP prophylaxis: HL, NHL, brain tumours, myelodysplasia, ALL, lymphoproliferative dz, or myeloma, relapsed dz, “high-dose” corticosteroids, or R-CHOP-14 regimen
– Treatment with 20 or more mg prednisone equivalent for 1 month or more
– Alemtuzumab or temozolomide recipients
– Allogenic and select autologous (w/purine analogue conditioning Tx) HCT recipients
– Solid organ transplant recipients
There are a few SMX/TMP regimens… DS tab daily, DS tab qMWF, SS tab daily… there isn’t much direction to choose one. There was an RCT in HIV-infected patients that wasn’t statistically significant for daily SMX/TMP, but there was roughly 2x more discontinuation due to ADRs from the daily group.
I’ve personally seen DS tab qMWF most but it all depends on patient-specific factors such as adherence and recent lab work!
Some causes of an elevated lactate include:
– Decreased renal function
– Comorbid liver disease
– Decreased tissue perfusion, hemodynamic instability (like sepsis)
– Active alcohol abuse
– Decompensated HF
– Hypoxic state
Myelodysplastic syndromes – risk and prognosis measured by DIPSS score, taking into account (one point each): age >65 yo, leukocytes >25, Plts <100, required transfusion, circulating blasts 1% or above, unfavourable karyotype, fever/sweats/wt loss preceding Dx. High risk DIPSS is for a score of 3 or above.
– DIPSS factors into decision making for drug therapy. High risk = allogenic HCT is favoured. Low risk = symptomatic care such as DNA hypomethylating agents, transfusion, G-CSF, or darbepoeitin may be favoured.
– Iron chelation therapy post-transfusion initiated if ferritin is constantly elevated >1000, AND pt is stable (no comorbid infections), DIPSS low risk (0-1) may favour iron chelation.
Few tidbits from the ADS on ID.
- Presence of polymorphonuclear cells (PMNs) indicates inflammation
- Beware of epithelial cell contamination in a sample
- Coagulase-negative Staphylococcus spp is often a contaminant of blood cultures
- A C&S will NEVER have PO susceptibility data due to concerns with bioavailability. Consult microbiology if you need direction.
- Eosinophilia increases suspicion of allergic reactions or parasitic infections
- Lymphocytosis increases suspicion of malignancy or bacterial infections
- Acute phase reactants are non-specific but add to the overall picture
- Pearl: cellulitis treated with ABX will appear to worsen for 2-3 days due to killing of bacteria and subsequent release of endotoxins
- Some antibiotics perform poorly in acidic environments, so therefore will not penetrate and treat an abscess.
- When do you consult microbiology?
- Need more specific identification on an organism
- Need additional susceptibility or MIC data
- Need guidance on which test to use to identify a bug
And of course, this fun gem: