Category Archives: Cardiology

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.

Push Dose Vasopressors

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Patient Case  

  • The team gets a call that there is a 75 year old male that triggered a sepsis alert in route with EMS and is currently desaturating on 15 L of oxygen with decision made to intubate this patient  
  • Prior to intubation, the patient hasn’t responded to  a NS bolus infusion these are the patient’s vitals: 
  • Knowing that pre-intubation hypotension has been associated with peri-intubation cardiac arrest, which agent do you order? If it is not commercially available, how do you make it?  

Pharmacology  

  Phenylephrine (PE)   Epinephrine (EPI)  
Properties   A1 ++++   ↑ BP   B1  ±        ↔HR   B2  ±      A1 +++      ↑ BP   B1 +++++   ↑ HR   B2 +++++  
Dose   100-200 mcg PRN Q 1-5 minute   10- 20 mcg PRN Q 1-5 minute  
Formulation   Premixed Syringe- 1000 mcg/10 ml   Not commercially available  
PK/PD   Onset: 1 minute   Duration: ~10-20 minutes   Onset: 1 minute   Duration: ~5-10 minutes  
Adverse Effects   Reflex bradycardia Hypertension   Tachycardia   Hypertension  
 Precautions   Bradycardia, heart block, heart failure, angina, acute MI   Tachycardia  
Compatibility   Compatible with NS, LR, D5   Compatible with NS, LR, D5  
Location in GHS   CPR, Trauma, Zone 2+3 Pyxis   1 mg/ml: CPR, Trauma, Zone 2+3 Pyxis  
Comments   Administer through a large bore peripheral IV; Low extravasation risk   Administer through a large bore peripheral IV; Low extravasation risk   
Making Epinephrine and Phenylephrine the “EASY WAY” Supplies: 10 ml of NS, Insulin syringe, epinephrine or phenylephrine vial, tape, pen Instructions:    Take an insulin syringe and draw up 0.1 ml of epinephrine 1 mg/ml or phenylephrine 10 mg/ml, dilute in 10 ml of NS, label epinephrine 10 mcg/ml (100 mcg total) or phenylephrine 100 mcg/ml (1000 mcg total) 
Making Epinephrine and Phenylephrine the Alternative Way   Epinephrine    Draw up 9 mL of normal saline into a 10 mL syringe (DO NOT use 10ml IV line “flush” syringes)  Into this syringe, draw up 1 mL of EPINEPHphrine 0.1 mg/mL (1 mg/10ml) from a cardiac syringe   Label syringe epinephrine 10 mcg/ml      Phenylephrine o Draw up 1 mL of phenylephrine from a 10 mg/mL vial into a 3 mL syringe o Inject this into a 100 mL bag of normal saline. Label bag; safely discard when finished  o Draw up 10 mL into a 10 mL syringe o Label syringe phenylephrine 100 mcg/ml         

Overview of Evidence  

Author, year    Design/ sample size   Intervention & Comparison   Outcome  
Rotando, 2019   Observational   ED/ICU   N=146   PE 100 mcg/ mL   or   Ephedrine 50 mg/10 mL   Most common indication = peri-intubation hypotension   Both agents associated with:   ↑ SBP by 26 mmHg   ↑ SBP by 26 mmHg   ↓ HR by 6 beats per minute   
Schwartz, 2016   Observational   ED   N=76   PE 100 mcg/ mL     (pre-filled syringe)      46.5%  patients were initiated on vasopressor drip ≤ 30 minutes;   mean MAP ↑ from 56.5 to 79.3 mmHg most common dose 100 mcg most common indication = peri-intubation hypotension  
Panchal, 2015   Observational   ED   N=119   PE 100 mcg/1 mL     PE given during the peri-intubation period: ↑ SBP by 20 mmHg, ↑ DBP by 10 mmHg, HR unchanged  
Doherty, 2012   RCT   OR   N=60   PE  IV push 120 mcg    (pre-filled syringe)   Vs    PE infusion @ 120 mcg/min   The infusion used more drug ( 1740 v 964  mcg)      Push dose pressor  had favorable impact of MAP compared to infusion   

References

  1. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved March 18, 2019, from http://www.micromedexsolutions.com/ 
  2. Scott Weingart. EMCrit Podcast 205 – Push-Dose Pressors Update. EMCrit Blog. Published on August 7, 2017. Accessed on March 19th 2019. Available at [https://emcrit.org/emcrit/push-dose-pressor-update/ ] 
  3. Holden D. Ann Emerg Med. 2018 Jan;71(1):83-92. 
  4. Panchal AR. J Emerg Med. 2015 Oct;49(4):488-94. 
  5. Rotando A. Am J Emerg Med. 2019 Mar;37(3):494-498. 
  6. Doherty A. Anesth Analg. 2012 Dec;115(6):1343-50. 
  7. Schwartz MB. Am J Emerg Med. 2016 Dec;34(12):2419-2422 

Sodium Bicarbonate in Cardiac Arrest

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Introduction

  1. Out-of-hospital cardiac arrest (OHCA) remains a leading cause of mortality and a substantial issue of public health concern worldwide.
  2. Sodium bicarbonate (SB) administration has been considered an important part of treatment for severe metabolic acidosis in cardiac arrest, because based on pathophysiologic considerations, normalization of extracellular and intracellular pH was considered a meaningful endpoint of resuscitation.
  3. Correction of metabolic acidosis with SB was recommended by early advanced cardiac life support (ACLS) guidelines published in 1973, and SB was the medication most frequently used during cardiac arrest until mid-1980s
  4. The 2010 ACLS Guidelines for adults published by the American Heart Association (AHA) state that “Routine use of sodium bicarbonate is not recommended for patients in cardiac arrest” (class lll recommendation, based on level of evidence (LOE) B)

Pharmacology

Dose 0.5-1 meq/kg/dose •     Repeat doses should be guided by arterial blood gases
Administration IV injection during cardiac arrest
PK/PD Onset Iv: Rapid Duration IV: 8-10mins Excretion: Urine (<1%)
Adverse Effects Hypocalcemia Intracellular acidosis (without adequate ventilation) HYPERNATREMIA Hyperosmosis Shift O2 release by hemoglobin
Compatibility Sodium bicarbonate solution may inactivate catecholamines such as epinephrine
  • May decrease of the biological effect of epinephrine to 77- 82 % of nonalkaline solution  
  • not powered

Overview of Evidence

Author, Year  Design/ sample size  NaHCO3 regimen   Outcome  
Chen YC, 2018  Observational/ n=5589   Not reported  Sodium bicarbonate during ED resuscitation was significantly associated with an increased rate of survival to hospital admission.  
Kawano T, 2017  Prospective observational/ n=13,865  Not reported   In OHCA patients, prehospital SB administration was associated with worse survival rate and neurological outcomes to hospital discharge.  
Ahn S, 2017  RCT/ n=50  50 mEq/L vs Placebo  No difference in sustained ROSC  (4% vs 16%) or good neurological outcome (0% vs 4% , p=.1)      SB had significant effect on pH (6.99 vs.   6.90, P=0.038) and bicarbonate levels   (21.0 vs. 8.0 mEq/L)  
Wang CH, 2016  Retrospective observational study/ n=109  Not Reported  SB was positively associated with sustained ROSC when serum potassium   level was <7.9 mEq in IHCA      Calcium and SB was positively associated with sustained ROSC when serum potassium level <9.4 mEq/L IHCA  
Vukmir RB, 2005  RCT/ n=792  1 mEq/kg NaHCO3  Overall survival rate was 13.9%      No difference in survival in those who   received bicarbonate      2-fold increase in survival in arrest >15 min (32.8 vs 15.4)*  
Bishop RL, 1976  Animal+human   case studies/ n=6  1 mEq/kg of 7.5% sodium bicarbonate in dogs      0.5-0.9 mEg/kg in humans  Animal 1 mEq/Kg   SB resulted in increases in the Pco2 (27→49),  pH (7.38 →7.56) and   the serum osmolality (309→349)      Man 0.5-0.9 mEq/Kg    SB resulted in increases in the Pco2 (24.5→38.8),  pH (7.23 →7.48) and the serum osmolality (308→343)  

References

  1. Sodium bicarbonate. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved October 11, 2018, from http://www.micromedexsolutions.com/ 
  2. Bishop RL, et al. Sodium bicarbonate administration during cardiac arrest. Effect on arterial pH PCO2, and osmolality. JAMA. 1976 Feb 2;235(5):506-9.
  3. Vukmir RB, et al. Sodium bicarbonate in cardiac arrest: a reappraisal. Am J Emerg Med. 1996 Mar;14(2):192206. 
  4. Vukmir RB, et al. Sodium bicarbonate improves outcome in prolonged prehospital cardiac arrest. Am J Emerg Med. 2006 Mar;24(2):156-61. 
  5. Wang CH,et al. The effects of calcium and sodium bicarbonate on severe hyperkalaemia during cardiopulmonary resuscitation: A retrospective cohort study of adult in-hospital cardiac arrest. Resuscitation. 2016 Jan;98:105-11. 
  6. Ahn S, et al. Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study. J Thorac Dis. 2018 Apr;10(4):22952302 
  7. Kawano T, et al. Prehospital sodium bicarbonate use could worsen long term survival with favorable neurological recovery among patients with out-of-hospital cardiac arrest. Resuscitation. 2017 Oct;119:63-69. 
  8. Chen YC, et al. The association of emergency department administration of sodium bicarbonate after out of hospital cardiac arrest with outcomes.  Am J Emerg Med. 2018 Mar 5. pii: S0735-6757(18)30187-6.