CICU Pharmacotherapy Myth-Busters

1. CICU PharmacotherapyMyth-Busters David Nelson, MD, PhD Medical Director, Cardiovascular Intensive Care UnitDivision of CardiologyCincinnati Children's Hospital Medical Center Jaclyn Sawyer, PharmD Clinical Pharmacy Specialist, Cardiology Division of Pharmacy Cincinnati Children's Hospital Medical Center

2. Myths • Calcium infusionsare not an effective inotrope • Intravenous Potassium replacement is more effective than enteral Potassium replacement • Economic Myths– Older drugs are cheaper – cost reality check

3. MYTH: Calcium infusionsare not an effective inotrope

4. Cardiomyocyte Calcium Concentration Contractility and Relaxation Neonatal Hearts DemonstrateMarkedly Increased Ca+2 Sensitivity • Mature mammalian myocytes => Sarcoplasmic reticulum • Sarcoplasmic reticulum is immature in neonatal hearts • Structurally and functionally under-developed Na/Ca Exchanger L-type Ca Channel

5. Calcium Chloride • Unique inotrope • Improves myocardial function with minimal change in heart rate minimizing myocardial oxygen demand => Improved cardiac output in patients with myocardial dysfunction with no increase in heart rate • Small incidence of non-cardiac side effects • Ongoing studies • Prospective • Safety

6. Calcium Chloride Infusions, Used as an Inotrope, Improve the Hemodynamics of Critically Ill Children • Calcium Chloride • Retrospective – CaCl for hemodynamic instability • 2.5-15 mg/kg/hr • May 2011-May 2012 • Efficacy at 2hrs and 6hrs • Heart Rate • Blood Pressure • Systemic arterial O2 and mixed venous O2 – AVO2 difference • NIRS • Lactate • Urine Output • Other inotropes • Safety Averin K. CCHMC data awaiting publication

7. Calcium Chloride Infusions Improve Cardiac Output: Baseline Characteristics LCO etiology: • Nonsurgical: 46% • Surgical: 53% (CHD) Averin K. CCHMC data awaiting publication

8. Calcium Chloride – HD Response 64% to 69% P<0.001 69 to 77 P<0.001 3.4 to 2.5 P<0.0001 Not significant 33% to 26% P<0.001 UOP increased by 29% in 8hr period after Ca initiation Averin K. CCHMC data awaiting publication

9. Calcium Chloride Infusions Improve Cardiac Output: Results • Baseline iCa does not change effect to Ca infusion • HD improvements did not correlate with higher iCa • All age groups had improvements CO measures • Neonates most robust • Single and Bi – ventricular groups both had improvements in CO • Surgical and non-surgical groups both had improvements in CO Averin K. CCHMC data awaiting publication

10. Calcium Infusion Considerations • Calcium Chloride vs Calcium Gluconate • calcium gluconate: 4.65 mEq Ca++/gram • calcium chloride: 13.6 mEq Ca++/gram • Safety monitoring • Pancreatic enzymes • Nephrolithiasis and nephrocalcinosis • Compatibility considerations • TPN

11. MYTH: Intravenous Potassium replacement is more effective than enteral Potassium replacement

12. Institute for Safe Medication Practices classifies Intravenous Potassium as a “High-alert” medication

13. ISMP - IV Potassium classified as “high alert medication” • Inappropriate administration can lead to serious adverse events such as cardiac arrest or death • 1980s-1990s - Concentrated KCl products removed from patient care areas • Commercially mixed solutions used when at all possible • Other safety measures • Standard concentrations • Double checks, infusion pump guardrails, storage precautions

14. Texas Children’s Hospital • Practice change: Enteral potassium supplementation preferred over IV unless severe GI disease (NEC, surgical abdomen) • IV: 1 mEq/kg/dose (max 40mEq/dose); 0.3mEq/mL over 1 hr • Enteral: 1 mEq/kg/dose (max 40mEq/dose) oral or NG; 2.67mEq/mL with SW eqvol for flush • Definitions: • Hypokalemia: <3.5 mmol/L • Hyperkalemia: >5.5 mmol/L Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5

15. Enteral Potassium SupplementationPatient Demographics • Treatment Bias • Preference of IV in patients on vasopressin Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5

16. Enteral Potassium Supplementation • Treatment Bias’ • Preference of IV in patients on vasopressin • Preference of IV in patients with lower potassium levels Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5

17. Enteral Potassium Supplementation • Enteral and intravenous potassium supplementation are equivalent • Other advantages beyond safety • Reduced fluid administration • Cost $ • Decreased resource utilization • Decrease frequency of IV line access • Too small to assess safety • No difference in potassium related ADE Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5

18. Enteral Potassium Supplementation • Enteral and intravenous potassium supplementation are essentially equivalent • Other advantages beyond safety • Reduced fluid administration • Example: 3 Kg infant, K Replacement 1mEq/Kg • Central IV Potassium: 15 mL • 0.2 mEq/mL (CCHMC standard concentration) • Peripheral IV Potassium: 75 mL • 0.04 mEq/mL (CCHMC standard concentration) • Enteral Potassium: 1.1 mL • 2.67mEq/mL Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5

19. Enteral Potassium Supplementation • Enteral and intravenous potassium supplementation are essentially equivalent • Other advantages beyond safety • Reduced fluid administration • Cost $ • Decreased resource utilization • Decrease frequency of IV line access • Too small to assess safety • No difference in potassium related ADE Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5

20. MYTH: Economic Myths- older drugs cost less money $ Cost Reality Check $

21. Older drugs cost less?Diuretics

22. Cost Reality CheckACE Inhibitors

23. Cost Reality CheckDexmedetomidine vs. Midazolam

24. Cost Reality Check • The Affordable Care Act and Accountable Care Organizations • Reduce expenditures and preserve or improve the quality of care

25. Summary – Myths-Busted!? • Calcium chloride infusions are effective in improving hemodynamics in patients with LCOS, with a low incidence of non-cardiac side effects and a trend towards a decrease in heart rate • Efficacy of enteral potassium is equivalent to that of intravenous potassium for potassium replacement in pediatric patients in the CICU • Due to the Affordable Care Act, costs of medications will become much more relevant to clinicians and Health Care Administrators

26. Thank you!Are there other Pharmacy-related myths to bust at your institution? David Nelson, MD, PhD Medical Director, Cardiovascular Intensive Care UnitDivision of CardiologyCincinnati Children's Hospital Medical Center Jaclyn Sawyer, PharmD Clinical Pharmacy Specialist, Cardiology Division of Pharmacy Cincinnati Children's Hospital Medical Center

27. FINAL MYTH: PHYSICIANS AND NURSE PRACTITIONERS HAVE ADEQUATE TRAINING IN PHARMACOLOGY and do not need Clinical pharmacists (pharm.d.) to provide optimal care.