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Pass Rates for the BCPS Exam: What You Need to Know

If you’re preparing for the Board-Certified Pharmacotherapy Specialist (BCPS) exam, you’re probably wondering what the pass rates are like. After all, knowing the pass rates can help you set realistic expectations and prepare more effectively. In this blog post, we’ll take a closer look at the pass rates for the BCPS exam and what you need to know.

Overall Pass Rates according to data from the Board of Pharmacy Specialties (BPS), the overall pass rate for the BCPS exam is around 55%. This means that slightly more than half of all test takers pass the exam. The numbers for first-time exam takers are slightly higher, with a pass rate of 69%.

While these pass rates may seem low, it’s important to remember that the BCPS exam is designed to be challenging. It’s meant to test your knowledge and skills in pharmacotherapy, and passing it is a significant achievement.

Content Outline changes one question that many BCPS exam takers have is whether there are any changes to the content outline for the exam. The last update to the content outline was in 2020, and since then, no major changes have been made. This means that you can expect the same number of questions from each topic area.

However, it’s worth noting that BPS historically updates the content outline for the exam every 3-5 years. While there are no planned changes for 2023, it’s possible that there may be changes in the coming years. It’s important to stay up-to-date on any changes to the content outline to ensure that you’re prepared for the exam.

Number of Questions and Exam Format the BCPS exam consists of 175 multiple-choice questions, with one answer for each question. You do not need to memorize brand names, as generic names are used in the exam.

You’ll have 4 hours and 23 minutes to complete the exam, which works out to about 1 minute and 30 seconds per question. This highlights the importance of setting a good pace and practicing with a practice exam to ensure that you’re comfortable with the time limit.

Conclusion: Preparing for the BCPS exam can be challenging, but knowing the pass rates and what to expect can help you prepare more effectively. With a pass rate of around 55%, it’s clear that passing the exam is a significant achievement. By staying up-to-date on any changes to the content outline and practicing with a practice exam, you can improve your chances of success on the exam.

Good luck!

Hypertonic Saline Versus Mannitol for ICP Reduction  

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Introduction  

  1. Elevated intracranial pressure (ICP) is caused by excess volume in the cerebral spaces, which causes a reduction in the cerebral perfusion pressure and affects blood flow and oxygenation to the brain.   
  2. Hyperosmolar agents (hypertonic saline and mannitol) are utilized to form a gradient across the blood-brain barrier to draw fluid from the cerebral space into the vasculature, thus reducing ICP  
  3. Mannitol was previously considered the gold standard of osmotic therapy, but hypertonic saline has proven to be at least as effective as mannitol at reducing ICP  

Pharmacology  

  Hypertonic Saline   Mannitol  
   Mechanism   Increases serum sodium levels, making it more hypertonic. Giving a bolus causes a gradient for   water to follow sodium extracellularly and move out   of the cerebral spaces into the vasculature, while a   continuous infusion aids in resuscitation   Osmotic diuretic by increasing the osmolality of the glomerular filtrate, thus blocking reabsorption of water and excretion of sodium. This leads to   movement of water to extracellular and vascular   spaces and reducing the ICP  
Dose  3 – 23.4% available      3%: optimal dose is unclear, reasonable to start with   300-500mL bolus or continuous infusion at 100mL/hr and titrate per response      23.4% : 0.43-0.5 mL/kg IV bolus, max 30mL/dose  5 – 25% solutions available (20% most common)      0.25 – 1g/kg/dose IV bolus q 6-8 hours (Usually 25-100g per dose)  
Administration  3% intermittent bolus or continuous infusion   *strong osmotic gradient not retained with continuous infusions      23.4% intermittent bolus over 15 minutes  Intermittent IV infusion over 30 minutes   
Adverse Effects  Hypervolemia,  respiratory distress, electrolyte imbalances (hypernatremia)  Hypotension, hypovolemia, AKI, electrolyte disturbances (specifically K+), extravasation  
Cautions/Pearls     Solutions > 3-5% require a central line      Requires in-line filter due to risk of crystallization Avoid in hypovolemia and anuria  
Patient population to consider use in  Hypovolemic, hypotensive, traumatic resuscitation   Euvolemia, hypertensive, fluid restrictions   
Monitoring  Serum sodium 145-155mEq/dL    Serum osmolality 300-320 mOsm/L Titrate based on ICP  Serum osmolality 300-320 mOsm/L  Titrated based on ICP  
Where to find in GHS  3% Sodium chloride – 500mL   EDZONE2, EDZONE3, ALL TRAUMA STATIONS  20% Mannitol – 500ML   EDZONE2, EDZONE3, TRAUMA-M, EDETENTION  

Considerations for Administration     

  3% Sodium Chloride  23.4% Sodium Chloride  20% Mannitol  
Vascular Access  Peripheral or central  Central ONLY  Peripheral or central  
Volume (per dose)  500mL +   ~30 mL  125 – 500 mL(20%)  
Equipment  Bolus: Infusion by gravity Continuous: IV infusion pump  Syringe pump preferred   IV infusion pump  

Overview of Evidence  

Author, year   Design/ sample   size  Intervention & Comparison  Outcome  
A. Kerwin, 2009  Retrospective analysis,  (22 patients)  HTS vs mannitol   mean ICP reduction in patients with TBI  HTS is as efficacious as mannitol, if not more so, and adds to the growing literature suggesting that HTS is an effective modality for the control of elevated ICP in patients with severe TBI  
M. Li, 2015  Meta-Analysis,    7 studies    (169 patients)  HTS vs mannitol in mean ICP reduction in patients with TBI  HTS reduces ICP more effectively than mannitol in the setting of TBI  
S. Burgess, 2016  Meta-Analysis,    7 trials    (191 patients)  HTS vs mannitol in mean ICP reduction, risk of ICP treatment  failure, mortality rates, and neurological outcomes  No statistical difference in mortality and neurological outcomes. No difference in mean reduced ICP; decreased risk of ICP treatment failure with HTS  
E. Berger- Pelleiter, 2016  Meta-Analysis,   11 studies   (1,820 patients)  HTS vs mannitol in reduction of mortality, ICP, and increasing functional outcomes  No significant reduction in mortality, no significant reduction in mean ICP, no significant difference in functional outcomes  
C.  Pasarikovski,  2017  Systematic   Review,   5 studies    (175 patients)  HTS vs mannitol in ICP reduction in aneurysmal subarachnoid hemorrhage  No difference between mannitol and 3% HTS in reducing ICP in patients with aneurysmal subarachnoid hemorrhage  
J. Gu, 2018  Mata-Analysis,   12 RCTs,    (438 patients)  HTS vs mannitol in ICP reduction, ICP control, changes in serum sodium and   osmolality, mortality,   neurological function  outcome  No difference in mean ICP reduction, neurological function, and mortality. HTS may be preferred in TBI patients with refractory intracranial hypertension  
It is essential to consider the adverse effects of each agent and the comorbidities for an individual patient rather than making a simple comparison in efficacy of hypertonic saline versus mannitol  

References

  • Burgess S, et al. Annals of pharmacotherapy. 2016;50(4):291-300.  
  • Li M, et al. Y, 2015. Medicine. 2015;9(4):17.  
  • Dastur C, et al. Stroke and vascular neurology. 2017;2:21-29.  
  • Kerwin A, et al. J Trauma. 2009;67:277-282.  
  • Pasarikovski C, et al. World Neurosurg. 2017;105:1-6.  
  • Gu J, et al. Neurosurg Rev. 2018;42:499.  
  • Berger-Pelleiter E, et al. CJEM. 2016;18:112–120.  
  • Farrokh S, et al. Curr opin crit care. 20119; 25:105-109.  
  • Witherspoon B, et al. Nurs Clin N Am. 2017;52:249-60.   
  • Micromedex [Electronic].Greenwood Village, CO: Truven Health Analytics. Retrieved August 12, 2019 from http://www.micromedexsolutions.com

10 Things You Can Do If You Don’t Match for a Pharmacy Residency Program

As pharmacy residency application season comes to a close, it’s time to take a deep breath and reflect on the experience. Regardless of the outcome, it’s important to remember that you’ve put in a tremendous amount of effort and dedication to get to this point.

Things didn’t go as planned but here’s 10 things you can do now to try to focus on what you can versus what you cannot.


10 Things to Do

  1. Do not panic or lose hope. Not matching is not the end of your career and there are still opportunities to pursue your goals
  2. Review your application materials and identify areas of improvement. Seek feedback from mentors, preceptors, faculty members, or peers who can help you improve your CV, letter of intent, interview skills, etc
  3. Consider participating in Phase II of the Match or the Post-Match Scramble. Phase II is another round of matching for programs that still have unfilled positions after Phase I. The Post-Match Scramble is an informal process where applicants can contact programs directly after Phase II to inquire about any remaining vacancies
  4. Be flexible and open-minded about your options. You may need to expand your geographic preferences, consider different types of programs or settings, or apply for non-traditional residencies such as fellowships or industry positions
  5. Network and stay connected with potential employers, mentors, preceptors, faculty members, alumni, or colleagues who can offer you advice, support, referrals, or opportunities.
  6. Update your online profiles and portfolios such as LinkedIn, ePortfolio, ASHP Connect etc., to showcase your achievements, skills, and interests.
  7. Seek out additional learning opportunities such as continuing education courses, certificate programs, webinars, podcasts, journals, etc., to enhance your knowledge and skills and demonstrate your commitment to professional development
  8. Explore alternative career paths or transitional roles that can help you gain valuable experience and exposure to different aspects of pharmacy practice such as clinical pharmacist, staff pharmacist, adjunct faculty member, consultant pharmacist, etc
  9. Maintain a positive attitude and a growth mindset. Do not let rejection or failure define you or discourage you from pursuing your goals. Learn from your mistakes and challenges and use them as opportunities to improve yourself
  10. Seek professional help or support if needed. Not matching can be a stressful and emotional experience that can affect your mental health and well-being. Do not hesitate to reach out to counselors, therapists, coaches, mentors, friends, family members, or other sources of support who can help you cope with your feelings and provide you with guidance and encouragement.

Good Luck with the next phase of your life

Fosphenytoin vs Keppra for Status Epilepticus

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Introduction

  1. Status epilepticus is a neurological emergency that required urgent assessment and treatment with pharmacologic agents
  2. Lorazepam and diazepam are short-acting drugs that can produce immediate effects.
  3. Treatment with another long-acting anticonvulsant drug is necessary to prevent recurrent convulsions.
  4. Use of IV phenytoin (PHT) in the treatment of status epilepticus dates back to the 50s with fosphenytoin (FPHT) being the primary agent in some institutions.
  5. However, both PHT and FPHT can induce adverse reactions such as a reduction in blood pressure, arrhythmia, and allergic symptoms.

Pharmacology

Properties  Phenytoin/ Fosphenytoin  Levetiracetam  (Keppra)  
Dose   20 mg/kg/PE   (max 1500 mg)  1-4.5 g IV   (40-60 mg/kg)*  
Administration  Max IV fusion   
PHT 50 mg/min   
FPHT 150 mg/min  		1g IV Push ~2 min**  
1.5-2g IV over 7 min**  
(2-5 mg/kg/min)  
Formulation  IV/PO  IV/PO  
PK/PD  Onset: ~30 min***  
Half Life: 12-28 hr
Excreted:  >90%   in urine  		Onset: 30-45 min  
Half-life: 6-8 hr  
Excreted: 66% renal  
Adverse Effect  Phlebitis, hypotension, bradycardia & dysrhythmias  Abnormal behavior   
Dizziness   
Irritability  
Drug   Interactions and warnings  Major CYP3A4 Inducer (↓ drug levels)  —–  
Compatibility  PHT – only D5W  
FPHT- D5W or NS  		D5W or NS  
 
*GHS has utilized this administration based on clinical experience 
**PE= Phenytoin equivalents  
** Fosphenytoin takes 15 mins to be metabolized to active metabolite in addition to the infusion time

Overview of Evidence

   Author,  Year  Design/ sample   size  Dosing regimen   Outcome  
ESETT  RCT   N= >  VPA 30 mg/kg (max 3000 mg)          vs   LEV 60 mg/kg (max 4500mg)         vs   PHT 20 mg/kg (max 1500 mg)  Result expected 2020  
Nakamura, 2017  *Respective analysis/ n=63  LEV 1000 mg            vs   FPHT 22.5 mg/kg   No difference in control of seizure(81 vs 85.1%, p=0.69), adverse effects, or transition to PO antiepileptic drug   
Gujjar et al, 2017  *Prospective,   open-label   trial/   n=52  LEV 30 mg/kg            vs   PHT 20 mg/kg  LEV displayed no statistically significant difference than PHT in SE       Sequential use of these 92–97% of case controlled without anesthetic agents.  
Chakravarthi, 2017  *RCT n=44  LEV 20 mg/kg               vs   PHT 20 mg/kg  Both LEV and PHT were equally effective at termination of seizure activity within 30min and recurrence of seizures within 24 hours  
Mundlamuri,  2015  RCT/ n=150  VPA  30 mg/kg            vs   LEV 25 mg/kg           vs   PHT 20 mg/kg  No statistically significant difference in control of SE between VPA (68%), PHT (68 %,) and LEV (78%).   
Alvarez et al, 2011  Retrospective  analysis/ n=466  VPA  20 mg/kg   LEV 20 mg/kg   PHT 20 mg/kg  VPA controlled SE in 74.6%, PHT in 58.6% and LEV in 51.7% of episodes       LEV failed more often than VPA [odds ratio (OR) 2.69  
* Did not reach power according to sample size analysis or did not mention in methods

References  

  1. Phenytoin. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved November 12, 2018, from http://www.micromedexsolutions.com/  
  2. Levetiracetam. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved November 12, 2018, from http://www.micromedexsolutions.com/  
  3. Alvarez V. Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam. Epilepsia. 2011 Jul;52(7):1292-6.
  4. Chakravarthi S. Levetiracetam versus phenytoin in management of status epilepticus. J Clin Neurosci. 2015 Jun;22(6):959-63.  
  5. Mundlamuri RC. Management of generalised convulsive status epilepticus (SE): A prospective randomised controlled study of combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or levetiracetam–Pilot study. Epilepsy Res. 2015 Aug;114:52-8.  
  6. Gujjar AR. Intravenous levetiracetam vs phenytoin for status epilepticus and cluster seizures: A prospective, randomized study. Seizure. 2017 Jul;49:8-12.  
  7. Nakamura K. Efficacy of levetiracetam versus fosphenytoin for the recurrence of seizures after status epilepticus. Medicine (Baltimore). 2017 Jun;96(25):e7206  
  8. Bleck T. The established status epilepticus trial 2013. Epilepsia. 2013 Sep;54 Suppl 6:89-92.  

Beyond Residency Applications: How to Focus on Self-Improvement and Growth

As pharmacy residency application season comes to a close, it’s time to take a deep breath and reflect on the experience. Regardless of the outcome, it’s important to remember that you’ve put in a tremendous amount of effort and dedication to get to this point. Now, it’s time to shift your focus to other areas of your life.

One of the most important things you can do during this time is to focus on yourself. This means taking the time to catch up on any projects, research, or top discussions that were put on hold due to residency application season. It also means making time for things outside of pharmacy, such as exercising, reading, or even binge-watching a new Netflix series.

By focusing on something outside of pharmacy, you can clear your mind and approach your work with a fresh perspective. People who are flexible, open-minded, and hard-working will make the best out of every situation and get more from a residency program than other candidates simply due to the fact that they have an open mindset compared to having a fixed mindset.

Residency training has gotten larger and more structured, which means that there will be a great program for you no matter where you end up. Trust that you got it right with your rank list, and that you will end up in the best scenario. Be open to learning and growing, and you will make the most out of your residency program.

And if you don’t match, that’s okay too. There are other routes you can take to get to the ultimate goal of using your pharmacy degree to the maximum and getting the job you desire. Don’t be discouraged – keep pushing forward and pursuing your dreams.

Remember, it’s important to take care of yourself and your well-being during this time. If you have any thoughts or comments, please feel free to share them with us in the comments section below. We’d love to hear from you.

Management of Hypertensive Emergency

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Introduction

  1. Hypertensive emergency is characterized by systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 120 mmHg with evidence of target organ damage. 
  2. Rapid blood pressure lowering with intravenous antihypertensives is warranted to prevent further organ damage. 
  3. Patients presenting with intracranial hemorrhage, aortic dissection, preeclampsia, or pheochromocytoma crisis should achieve target blood pressure within one hour of presentation. 
  4. Current literature lacks evidence of mortality benefit with any one antihypertensive drug. Selection of a medication should consider target organ(s) affected, underlying disease states, and time to target blood pressure. 

Treatment in Selected Co-Morbidities

ConditionBP GoalPreferred Agents
Acute aortic dissection  SBP < 120 mmHg within 20 minEsmolol Labetalol Nicardipine Nitroprusside
Eclampsia or Preeclampsia  SBP < 140 mmHg  within 1 hourNicardipine Labetalol Hydralazine
Pheochromocytoma (catecholamine excess)  SBP < 140 mmHg  within 1 hourNicardipine Phentolamine*
Intracranial hemorrhageSBP < 160 mmHg within 6 hoursNicardipine Labetalol
Acute ischemic strokePre-alteplase: < 185/110 mmHg Post-alteplase: < 180/105 for 24 hours No thrombolytic: SBP reduced 15% in 24 hours**                                                                       Nicardipine Labetalol
*Phentolamine currently unavailable due to nationwide shortage
**Permissive hypertension may be reasonable; maintain SBP < 220 mmHg or DBP < 120 mmHg

Pharmacology: Intravenous Antihypertensives

 First-line Agents 
MedicationClassOnsetDurationDosingClinical Pearls
Nicardipine    Ca channel blocker IV: 5-10 minIV: 2-6 hoursInitial: 5 mg/hr  Titration: 2.5 mg/hr every 15 min  Maximum: 15 mg/hr No dose adjustments in elderly patients 
Esmolol            Beta-blocker IV: 1-2 minIV: 10-20 minBolus: 500-1,000 mcg/kg Initial: 50 mcg/kg/min  Titration: repeat bolus dose, then increase by 50 mcg/kg/ min every 10 min Maximum: 200 mcg/kg/min Contraindications:  Bradycardia Decompensated HF 
Labetalol    Beta-blocker  Alpha-1 antagonistIV: 2-5 min Peak: 5-15 minIV: 2-6 hours Peak: 18 hoursBolus: 10-20 mg IV push every 10 min IV infusion: 0.5 – 10 mg/min titrated 1-2 mg/min every 2 hours Maximum: 300 mg total Precaution: Second-/thirddegree heart block Bradycardia Heart failure
 
Second-line Agents		 
Phentolamine*Non-selective alpha antagonistIV: SecondsIV: 15 min  Initial: 5 mg IV push  May repeat every 10 min PRN  Useful in catecholamine excess and clonidine withdrawal 
  Nitroglycerin        NOdependent vasodilatorIV: 2-5 minIV: 5-10 minACS: Initial: 5 mcg/min  Titration: 5 mcg/ min every 3-5 min Maximum: 20 mcg/min  Pulmonary edema: Initial: 100-200 mcg/min Titration: 50 mcg/min every 3-5 min Maximum: 400 mcg/minIndicated in ACS or pulmonary edema  Use caution in volume-depleted patients 
Sodium nitroprusside    NOdependent vasodilatorIV: SecondsIV: 1-2 minInitial: 0.3-0.5 mcg/kg/min  Titration: 0.5 mcg/kg/min every 1 min Maximum: 10 mcg/kg/min Requires intra-arterial BP monitoring   Tachyphylaxis and cyanide toxicity with prolonged use – Limit treatment duration
Hydralazine  Direct vasodilatorIV: 10 min IM: 20 minIV: 1-4 hours IM: 2-6 hoursInitial: 10-20 mg IV push  Repeat every 4-6 hours PRN Not available as an IV infusion 
Enalaprilat        ACE inhibitorIV: 15-30 minIV: 12-24 hoursInitial: 1.25 mg IV over 5 min  Titration: increase by 5 mg every 6 hours as needed Slow onset (~15 min)  Contraindications:  Pregnancy MI Bilateral renal stenosis 
*Phentolamine currently unavailable due to nationwide shortage

Overview of Evidence

Author (Title), Year DesignPurposeOutcome
Anderson (INTERACT), 2008RCT (N=404)Comparison of BP goals  (SBP < 140 vs SBP < 180)  in patients with acute ICHMean hematoma expansion was smaller in the intensive group (13.7% vs 36.3%) No difference in death or disability at 3 months (48% vs 49%) Limitation: included patients with SBP > 150 mmHg, over 30% of patients were treated with oral antihypertensive therapy
Quereshi (ATACH-2), 2016RCT (N=1,000)Comparison of BP goals  (SBP 110-139 vs SBP 179-140)  in patients with acute ICHAll patients received nicardipine infusion No difference between death or disability at 3 months (38.7% vs 37.7%) Increased renal adverse events within 24 hours in the intensive group (9.0% vs 4.0%) Limitation: mean SBP differed by only 10 mmHg between groups 2 hours post-randomization (129 mmHg vs 141 mmHg)
Peacock (CLUE), 2011RCT (N=226)Nicardipine IV infusion versus labetalol IV bolus for management of hypertensive emergencyPatients receiving nicardipine were more likely to reach target BP within 30 min (91.7% vs 82.5%) Rescue antihypertensive use did not differ significantly between groups within first 6 hours Limitation: only 63.3% of patients had evidence of target organ damage at randomization
Yang, 2004Prospective cohort (N=40)Nitroprusside IV versus nicardipine IV for hypertensive emergency with pulmonary edemaNo significant difference between blood pressure readings across groups at any time point No adverse events reported in either group Limitation: nicardipine dosing started at 3 mcg/kg/min (12.5 mg/hr in a 70 kg patient)

Conclusions

  1. Selection of a first-line antihypertensive should consider compelling indications and acute blood pressure goals, as robust literature comparing long-term outcomes across drug classes is lacking for most indications.
  2. Nicardipine may provide more consistent blood pressure control than labetalol. This is particularly important in patients with acute stroke, as large fluctuations in blood pressure are believed to negatively impact cerebral perfusion.
  3. Aggressive lowering of SBP less than 140 mmHg in patients with acute ICH has not been shown to improve long-term outcomes and may negatively impact renal perfusion. 
  4. Nicardipine has been shown to provide similar blood pressure control to nitroprusside. In patients with acute ICH, nitroprusside use within 24-hours of presentation was associated with higher in-hospital mortality. 

References

  1. Whelton, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Amer Heart Assoc 2018;71(6):e13-e115. 
  2. Benken ST. Hypertensive emergencies. CCSAP 2018;1:7-30.
  3. Anderson, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol 2008;7:391-9. 
  4. Quereshi, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. New Engl J Med 2016;375(11):1033-43. 
  5. Peacock WF, et al. CLUE: a randomized comparative effectiveness trial of IV nicardipine versus labetalol use in the emergency department. Critical Care 2011;15(R157):1-8. 
  6. Yang HJ, Kim JG, Lim YS, et al. Nicardipine versus nitroprusside infusion as antihypertensive therapy in hypertensive emergencies. J Int Med Res 2004;32:118-23. 

Fibrinolytics for STEMI

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Introduction

  1. Percutaneous coronary intervention (PCI) is the preferred reperfusion strategy during a cardiac arrest; thrombolytic therapy is an option without PCI capability, followed by transfer to a PCI capable center. 
  2. Thrombolytic therapy is most effective when administered within 30 minutes of first medical contact, however, may be considered within 12 – 24 hours of symptom onset and ongoing ischemia or extensive ST elevation. 
  3. During ACS-Induced Cardiac Arrest, the goal for fibrinolysis is 30 minutes and reperfusion with PCI is preferred, however, if PCI is delayed, fibrinolytics therapy could be considered.

Pharmacology

 AlteplaseTenecteplase
MOAInitiates fibrinolysis by binding to fibrin in a thrombus and converts entrapped plasminogen to plasmin Promotes initiation of fibrinolysis by binding to fibrin and converting plasminogen to plasmin; similar to alteplase but more fibrin specific 
DoseWeight based: > 67kg: infuse 15mg IV bolus over 1-2 minute, followed by 50mg infusion over 30 minutes, then 35mg over 1 hour (max total dose 100mg)   ≤ 67kg: : infuse 15mg IV bolus over 1-2 minutes, followed by 0.75mg/kg infusion over 30 minutes, then 0.5mg/kg over 1 hour (max total dose 100mg)Weight based: < 60kg: 30mg  ≥ 60 to < 70kg: 35mg ≥ 70 to < 80kg: 40mg  ≥ 80 to < 90kg: 45mg  ≥ 90kg: 50mg 
Administration•      Bolus administered over 1 minute followed by infusion •      Single bolus over 5 seconds 
PK/PDDuration: 1 hour after infusion terminated  Distribution: approximates plasma volume Half-life elimination: 5 minutes  Excretion: hepatic and plasma clearance Distribution: weight related  Metabolism: hepatic  Half-life elimination: biphasic; initial 20-24 min, terminal 90-130 min  Excretion: plasma clearance 
Adverse EffectsIntracranial hemorrhage Ecchymosis  GI/GU hemorrhage  Sepsis  Cerebrovascular accident Hemorrhage and hematoma  Cerebrovascular accident
Drug Interactions and WarningsTranexamic acid, avoid combination  Internal bleeding, thromboembolic events, cholesterol embolization Tranexamic acid, avoid combination  Internal bleeding, thromboembolic events, arrhythmias
Contraindications Active internal bleeding  Ischemic stroke within 3 months except when within 4.5 hours Severe uncontrolled hypertension Active internal bleeding Severe uncontrolled hypertension Recent intracranial/intraspinal surgery Ischemic stroke within 3 months
Compatibility    May be diluted in equal volume with: 0.9% sodium chloride  D5W•      Incompatible with dextrose 

Overview of Evidence

Author, year Design/ sample sizeIntervention & ComparisonOutcome
Guillermin 2016aMeta-analysis of RCT (n=18,208)•      Tenecteplase 30-50mg vs alteplase 80-100mg Bleeding 4.8% in tenecteplase vs 5.8% alteplase (p=0.0002)  No difference in mortality at 30 days 
 Llevadot 2001 Retrospective review (38 studies) Reteplase Anoteplase TenecteplaseTenecteplase and reteplase associated with accelerated infusion and more convenient by bolus administration  Administration of a less fibrin-specific agent may cause greater systemic coagulopathy with potential for more bleeding 
Boersma 1996Retrospective review (n=50,246) •      Fibrinolytic therapy vs placebo •      Mortality reduction in patients treated within 2 hours compared to later (p=0.001) 
GUSTO 1993Randomized, controlled trial (n=41,021) Streptokinase + SQ heparin Streptokinase + IV heparin Alteplase + IV heparin Alteplase + Streptokinase + IV heparin  Atleplase administered over 1.5 hours with IV heparin provide survival over standard therapy Thrombolytic therapy administered within 2448 hours of admission  
Armstrong 2013bRandomized controlled trial (n=1892)•      PCI vs bolus tenecteplase, clopidogrel, and enoxaparin Tenecteplase administration prehospital resulted in effective reperfusion when PCI was not completed within 1 hour  Fibrinolytic therapy associated with increase risk of intracranial bleeding 
  Cardiac Arrest Data
Bottiger 2001Prospective cohort (n=40)•      Alteplase 50 mg bolus, repeat 50 mg in 30 minutes vs placebo•      Increase in ROSC (68% vs 44%), ICU admission compared to placebo
Schreiber 2002Retrospective chart review (n=157) •      Alteplase 15mg bolus followed by 50mg infusion over 30 min and 35mg over 60 min•      Thrombolytic therapy achieved better functional neurological recovery more frequently (p=0.03) 
Lederer 2004Retrospective chart review (n=108)•      Alteplase 100 mg (15 mg followed by 85 mg over 90 min)81% of patients who received thrombolytic therapy were discharged without neurological deficit  67% of patients were still alive 5-10 years after the event 
Li 2006Meta-analysis•      Alteplase 15mg bolus followed by 50mg infusion over 30 min and 35mg over 60 minThrombolytic therapy improved the rate of ROSC (p < 0.01)  48% of patients had acute coronary artery obstruction 
Bottiger 2008Randomized, double-blind, multicenter trial (n=1050)Tenecteplase 30mg if < 60kg Tenecteplase 35mg if 60-69kg  •                 Tenecteplase 40mg if 70-79kg  Tenecteplase 45mg if 80-89kg  Tenecteplase 50mg if > 90kg  Placebo No difference in tenecteplase and placebo in 30-day survival, ROSC, survival, or neurologic outcomes  Increased intracranial hemorrhages in tenecteplase patients
RuizBailen 2001Retrospective cohort (n=303) Streptokinase  Alteplase accelerated regimen  Alteplase double bolus Systemic thrombolysis patients had a lower mortality, less mechanical ventilation, fewer CPR attempts (p < 0.0001)  No fatal hemorrhagic complications 
aAdministered as tenecteplase 30-50mg bolus and alteplase 15mg bolus followed by 0.75mg/kg infusion over 30 min  bHalf-dose tenecteplase administered in patients ≥ 75 years old cReteplase administered as two boluses of 10 million units given 30 minutes apart 

Conclusions

  1. Evidence supports PCI is the first line option for management of patients requiring reperfusion during cardiac arrest when a STEMI is suspected 
  2. Available evidence suggests tenecteplase and alteplase are appropriate fibrinolytic therapies when PCI is unavailable
  3. Tenecteplase is an alternative fibrinolytic therapy and has been evaluated safe and efficacious as a bolus dose of 30-50mg
  4. When alteplase is the only fibrinolytic therapy available, there is data to support bolus therapy +/-  a weight based infusion during cardiac arrest
  5. Thrombolytic agents administered during CPR can improve the rate of survival but are associated with a risk of severe bleeding 

References

  1. Lexicomp [Electronic version]. Macedonia, OH: Truven Wolters Kluwer Health. Retrieved January 26, 2021, from https://online.lexi.com/lco/action/login.
  2. Guillermin A, Yan D, Perrier A, Marti C. Safety and efficacy of tenecteplase versus alteplase in acute coronary syndrome: a systematic review and meta-analysis of randomized trials. Arch Med Sci 2016; 12, 6: 1181–1187.
  3. Llevadot J, Giugliano R, Antman E. Bolus fibrinolytic therapy in acute myocardial infarction. JAMA. 2001; 286(4): 442-449.
  4. Boersma E, Maas A, Deckers J, Simoons M. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet. 1996; 348: 771-775. 
  5. GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. NEJM. 1993; 329(10): 673-682. 
  6. Armstrong P, Gershlick A, Goldstein P, Wilcox R, Danays T, Lambert Y, Sulimov V, Ortiz F, Ostojic M, Welsh R, Carvalho A, Nanas J, Arntz H, Halvorsen S, Huger K, Grajek S, Fresco C, Bluhmki E, Regelin A, Vandenberghe K, Bogaerts K, de Werf F. Fibrinolysis or primary PCI in STSegment elevation myocardial infarction. NEJM. 2013; 268(15):1379-1387. 
  7. Wilcox R. Randomized, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. Lancet. 1995; 346(8971):329-336.  
  8. Van de Werf F, Cannon CP, Luyten A, Houbracken K, McCabe CH, Berioli S, Bluhmki E, Sarelin H, Wang-Clow F, Fox NL, Braunwald E. Safety assessment of single-bolus administration of TNK tissue-plasminogen activator in acute myocardial infarction: the ASSENT-1 trial. The ASSENT-1 Investigators. Am Heart J. 1999 May;137(5):786-91. doi: 10.1016/s0002-8703(99)70400-x. PMID: 10220625.
  9. Lederer W, Lichtenberger C, Pechlaner C, et al. Recombinant tissue plasminogen activator during cardiopulmonary resuscitation in 108 patients with out-of-hospital cardiac arrest. Resuscitation. 2001;50(1):71—76.
  10. Schreiber W, Gabriel D, Sterz F, et al. Thrombolytic therapy after cardiac arrest and its effect on neurological outcome. Resuscitation. 2002;52(1):63—69.
  11. Lederer W, Lichtenberger C, Pechlaner C, et al. Longterm survival and neurological outcome of patients who received recombinant tissue plasminogen activator during out-of-hospital cardiac arrest. Resuscitation. 2004;61(2):123—129.
  12. Li X, Fu QL, Jing XL, et al. A meta-analysis of cardiopulmonary resuscitation with and without the administration of thrombolytic agents. Resuscitation. 2006;70(1):31—36.
  13. Bottiger BW, Arntz HR, Chamberlain DA, et al. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. NEJM. 2008;359(25):2651—2662.
  14. Kurkciyan I, Meron G, Sterz F, et al. Major bleeding complications after cardiopulmonary resuscitation: impact of thrombolytic treatment. J Intern Med. 2003;253(2):128-135.
  15. Ruiz-Bailén M, Aguayo de, Serrano-Córcoles M, Diáz-Castellanos M, Ramos-Cuadra J, Reina-Toral A. Efficacy of thrombolysis in patients with acute myocardial infarction requiring cardiopulmonary resuscitation. Intensive Care Med. 2001;27(6): 1050-1057.
  16. Richling N, Herkner H, Holzer M, Riedmueller E, Sterz F, Schreiber W. Thrombolytic therapy vs primary percutaneous intervention after ventricular fibrillation cardiac arrest due to acute ST-segment elevation myocardial infarction and its effect on outcome. Am J Emerg Med. 2007 Jun;25(5):545-50. doi: 10.1016/j.ajem.2006.10.014. PMID: 17543659.
  17. Böttiger B, Bode C, Kern S, et al. Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial. Lancet. 2001;357(9268):1583-1585.

Procainamide for Wide Complex Tachycardia

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Introduction

  1. Ventricular tachycardia (VT) is an uncommon but dangerous medical condition, with an extremely variable clinical presentation.
  2. Intravenous procainamide is guideline recommended and is the drug of choice for the treatment of hemodynamically stable VT with a class IIa recommendation.
  3. Procainamide is an old drug with new evidence that supports it’s use but dosing strategies and administration techniques makes it difficult to use at the bedside.

Pharmacology

  Procainamide
Dose and administration
  • Bolus Dosing
    • 10-17 mg/kg over 20-60 minutes (Max dose suggest 1g and max rate of 20-50 mg/min)                   
    • alternative Dosing: 100 mg every 5 minutes at max rate of 50 mg/min to max dose 1g 
  • Renal Adjustments
    • eCrCl 10-50 ml/min: Reduce initial dosing by 25-50 %
    • eCrCL < 10 ml/min: Reduce initial dosing by 50-75%  
  • Maintenance Infusion Dosing 1-6 mg/min 
Mechanism of Action  •      Class 1A anti-arrhythmic that binds to fast sodium channels inhibiting recovery after repolarization. It also prolongs the action potential and reduces the speed of impulse conduction
PK/PD
  • Onset: IV <2 minutes; IM 10-30 minutes
  • Time to Peak: IV 25-60 minute; IM 15-60 minutes
  • Duration: IV/IM: 3-4 hours
  • Metabolism: Converted by the liver to N-acetylprocainamide (NAPA), an active compound
  • Half-life: 2.5– 4.7 hr (NAPA— 7 hr); increased in renal impairment
  • Excretion: 40– 70% excreted unchanged by the kidneys
Adverse Effects Hypotension Hepatotoxicity Positive ANA titer Lupus-like syndrome Anaphylaxis caused by sulfite salt Myasthenia gravis exacerbation  Angioedema
Drug Interactions and warnings         •      Interacts with diazepam, diltiazem, milrinone, phenytoin, and hydralazine
Compatibility Compatible in  o                0.9 % Sodium Chloride and 0.45% sodium chloride,  Incompatible with  o        D5 (depending on procainamide concentration), LR, and D5NS 
Comments •      Define hospital’s dosing and administration policy as there is a risk for adverse event’s due to multiple dosing strategies in the literature

Overview of Evidence

Author, year  Design/ sample size Intervention & Comparison Outcome
Ortiz,2017 Randomized controlled trial   n= 62 IV procainamide 10 mg/kg over 20 min IV amiodarone 5mg/kg over 20 min Major cardiac adverse occurred in 3 of 33 (9%) procainamide and 12 of 29 (41%) amiodarone patients.   Tachycardia terminated within 40 min in 22 (67%) procainamide and 11 (38%) amiodarone patients. 
Maril,2010 Multicenter cohort study    n= 187 IV Amiodarone 2 mg/kg infusion at a rate of at least 10 mg⁄ min   IV Procainamide 10 mg/kg infusion at a rate of at least 15 mg⁄ min •      The rates of VT termination were 25% (13 ⁄ 53) and 30% (9 ⁄ 30) for amiodarone and procainamide, respectively.
Komura,2010 Retrospective analysis   n= 90 IV Procainamide 100 mg over 1–2 min   IV Lidocaine bolus of 50 mg •      Procainamide and lidocaine terminated VTs in 53/70 (75.7%) and in 7/20 (35.0%) respectively.
Maril,2006 Retrospective case series   n= 33 IV Amiodarone 150 mg over 15 minutes Amiodarone rate of successful ventricular tachycardia termination was 8 of 28 (29%).   Two of 33 patients (6%) required direct current cardioversion for presyncope or hypotension temporally associated with amiodarone treatment.
Gorgels,1996 Randomized parallel study   n= 79 IV Procainamide 10 mg/kg   IV Lidocaine 1.5 mg/kg Lidocaine terminated 6 of 31 VTs and procainamide 38 of 48 (p <0.001).    A comparison of the QRS width and QT interval before and at the end of the injection revealed significant lengthening of these values after procainamide but no change after lidocaine.
Callans,1992 Observational study   n= 15 IV Procainamide rate of 50 mg/min until the arrhythmia terminated or a total dose of 15 mg/kg  •      Procainamide was well tolerated and resulted in termination of ventricular tachycardia in 93% of patients after administration of 100 to 1,080 mg (median dose 600 mg).

References

  1. Procainamide. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved July 6, 2020, from http://www.micromedexsolutions.com/
  2. Long B, Koyfman A. Best Clinical Practice: Emergency Medicine Management of Stable Monomorphic Ventricular Tachycardia. J Emerg Med 2017;52:484-492.
  3. Ortiz M, Martín A, Arribas F, et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. Eur Heart J. 2017;38(17):1329-1335. doi:10.1093/eurheartj/ehw230
  4. Marill KA, deSouza IS, Nishijima DK, et al. Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison. Acad Emerg Med. 2010;17(3):297-306. doi:10.1111/j.1553-2712.2010.00680.x
  5. Komura S, Chinushi M, Furushima H, et al. Efficacy of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Circ J. 2010;74(5):864-869. doi:10.1253/circj.cj-09-0932
  6. Marill KA, deSouza IS, Nishijima DK, Stair TO, Setnik GS, Ruskin JN. Amiodarone is poorly effective for the acute termination of ventricular tachycardia. Ann Emerg Med. 2006;47(3):217-224. doi:10.1016/j.annemergmed.2005.08.022
  7. Gorgels AP, van den Dool A, Hofs A, et al. Comparison of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Am J Cardiol. 1996;78(1):43-46. doi:10.1016/s0002-9149(96)00224-x
  8. Callans DJ, Marchlinski FE. Dissociation of termination and prevention of inducibility of sustained ventricular tachycardia with infusion of procainamide: evidence for distinct mechanisms. J Am Coll Cardiol. 1992;19(1):111-117. doi:10.1016/0735-1097(92)90060-z
  9. Wellens HJ, Bär FW, Lie KI, Düren DR, Dohmen HJ. Effect of procainamide, propranolol and verapamil on mechanism of tachycardia in patients with chronic recurrent ventricular tachycardia. Am J Cardiol. 1977;40(4):579-585. doi:10.1016/0002-9149(77)90074-1

Digoxin Poisoning Management

Digoxin Poisoning Management

Pharmacy Friday Pearl – Pharmacy & Acute Care University

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Introduction

  • Digoxin treats atrial flutter, atrial fibrillation, and heart failure.
  • Toxicity occurs when Na+/K+-ATPase inhibition raises intracellular Na+/Ca2+, triggering dysrhythmias.
  • EKG red flags: PVCs, biphasic T waves, shortened QT interval, variable AV block.
  • Therapeutic range 0.8 – 2.0 ng/mL; toxicity often begins > 2 ng/mL.

Digoxin Immune Fab (DigiFab / DigiBind)

Parameter Key Details
Dose 1 vial = 40 mg (binds 0.5 mg digoxin).
Unknown ingestion → 10-vial empiric dose.
Alternative: vials = 2 × total body load (mg).
Chronic unknown: adults 3 – 6 vials; children 1 – 2 vials.
Administration IV infusion over 30 min (rapid bolus if arrest imminent).
Onset / Duration Onset 20 – 90 min • Duration 15 – 20 h.
Adverse Effects Orthostatic hypotension, ventricular tachycardia, hypokalemia.
Mechanism Fab fragments swiftly bind circulating digoxin, neutralising toxicity.
Compatibility Compatible only with 0.9 % sodium chloride.

Clinical pearl: monitor serum K+ closely—intracellular shifts often trigger hypokalemia post-Fab.

Overview of Key Evidence

Author / Year Design (n) Key Findings
Wei 2021 Case series (121) FAERS: DigiBind serious AEs 87 % vs DigiFab 63 %; hypotension, cardiac arrest, death most frequent.
Ward 2000 Observational (16) Both Fab products reduced free digoxin below assay limits; total digoxin ↑ ≈10-fold (binding confirmed).
Renard 1997 Observational (16) Fab clearance declined linearly with renal impairment & age; t½ 11 – 34 h; all patients recovered without AEs.
Antman 1990 Open-label (150) 90 % toxicity resolved/improved; median dose 5 vials (200 mg); maximum 40 vials.
Roberts 2016 Systematic review Fab therapy remains first-line; hyperkalemia & ventricular arrhythmias are key toxicity predictors.
Ujhelyi 1995 PK review Fab exhibits two-compartment kinetics; repeat dosing may be needed in large body-load poisonings.

Clinical Conclusions

  • Digoxin toxicity is life-threatening but rapidly reversible with Digoxin Immune Fab.
  • If the ingested amount is unknown, administer an empiric 10-vial dose.
  • Do not delay Fab therapy for age- or renal-based calculations.

Full Reference List

  1. Bismuth C, Gaultier M, Conso F, Efthymiou ML. Hyperkalemia in acute digitalis poisoning. Clin Toxicol. 1973;6(2):153-162.
  2. David MNV, Shetty M. Digoxin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
  3. Lexicomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc. January 2023.
  4. Antman EM et al. Treatment of life-threatening digitalis intoxication with digoxin-specific Fab fragments. Circulation. 1990;81(6):1744-1752.
  5. Renard C et al. Pharmacokinetics of digoxin-specific Fab: effects of renal function & age. Br J Clin Pharmacol. 1997;44(2):135-138.
  6. Roberts DM et al. Pharmacological treatment of cardiac glycoside poisoning. Br J Clin Pharmacol. 2016;81(3):488-495.
  7. Ujhelyi MR, Robert S. Pharmacokinetic aspects of digoxin-specific Fab therapy. Clin Pharmacokinet. 1995;28(6):483-493.
  8. Wei S et al. Adverse events with digoxin Immune Fab in FAERS 1986-2019. Drugs - Real World Outcomes. 2021;8:253-262.
  9. Ward SB et al. Pharmacokinetics & bioaffinity of DigiTAb vs Digibind. Ther Drug Monit. 2000;22(5):599-607.