Vasopressin Use in Pediatric cardiac arrest

1. Vasopressin Use in Pediatric cardiac arrest Brandy Bratcher, PharmD PGY2 Pharmacy Resident St. Louis Children’s Hospital

2. Review common causes of cardiac arrest in pediatric patients • Discuss the current standard of care for cardiac arrest in pediatric patients • Analyze the role of vasopressin in the treatment of cardiac arrest in adult patients • Evaluate the role of vasopressin in the treatment of cardiac arrest in pediatric patients

3. Cardiac Arrest Incidence • Cardiac arrest occurs in 8-20 per 100,000 children annually • Cardiac arrest occurs in 36-81 per 100,000 adults annually Topjian AA et al. Pediatrics. 2008; 122(5): 1086-95.

4. In-Hospital Survival Rates • Return of spontaneous circulation (ROSC) is achieved in 66% of patients • Survival to hospital discharge is 27% • 75% of these patients have normal neurological function or mild disability Topjian AA et al. Pediatrics. 2008; 122(5): 1086-95.

5. Out-of-Hospital Survival Rates • Survival to hospital discharge is < 10% • 50% of these patients have normal neurological function or only mild disability • Only 30% of cases are provided with bystander cardiopulmonary resuscitation (CPR) attributing to lower survival rates Topjian AA et al. Pediatrics. 2008; 122(5): 1086-95.

6. Pediatric Cerebral Performance Category Score (CPCS) Fisher DH. Assessing the outcome of pediatric intensive care. J Pediatr. 1992; 121: 68-74.

7. Risk Factors for Poor Outcomes • Environment where arrest occurs • Pre-existing conditions • Duration of pulseless arrest without CPR • Initial electrocardiographic (EKG) rhythm • Quality of advanced life support interventions

8. Global ischemia Direct cellular damage and edema Edema in the brain can caused increased ICP and decreased cerebral perfusion Decreased ATP production Loss of membrane integrity Inflammatory response Microvascular thrombosis and loss of vascular integrity Apoptosis Accelerated cell death Pathophysiology of Cardiac Arrest

9. Causes of Pediatric Cardiac Arrest • Respiratory failure (most common) • Cardiac insufficiency • Miscellaneous

10. Respiratory Failure • Upper airway obstruction • Restrictive airway disease • Asthma • Cystic fibrosis (CF) • Bronchopulmonary dysplasia (BPD) • Impaired air exchange • Pneumonia • Surfactant deficiency

11. Cardiac Insufficiency • Congenital Heart Disease • Coronary Arterial Disease • Myocardial Disease • Conduction System Abnormality/Arrhythmia

12. Miscellaneous • Electrolyte disturbances • Hyperkalemia, hypokalemia, hypomagnesemia • Pulmonary hypertension • Inborn errors of metabolism • Sudden infant death syndrome (SIDS) • Hypothermia • Commotio cordis • Non-accidental trauma • Poisoning

13. Phases of Cardiac Arrest & Resuscitation • Pre-arrest (Protect) • Early recognition of respiratory failure and/or shock to prevent cardiac arrest • No flow (Preserve) • Initiate CPR and defibrillation (if indicated) • Low flow (Resuscitate) • Utilize effective CPR techniques • Administer medication therapy as indicated by PALS • Post-Resuscitation (Regenerate) • Optimize cardiac output and perfusion • Treat underlying conditions

14. Resuscitation Guidelines • Advanced Cardiac Life Support (ACLS) • Pediatric Advanced Life Support (PALS) • Neonatal Resuscitation Program (NRP)

15. Timeline 1960 1970 1980 1990 2000 2010 Intracardiac epinephrine 1st ACLS guideline (1974) Epinephrine in cardiac arrest PALS (1983) & NRP (1987) guidelines

16. Pediatric Advanced Life Support (PALS) American Heart Association. Management of Cardiac Arrest. Circulation 2005; 112: 167-187.

17. Timeline 1960 1970 1980 1990 2000 2010 Intracardiac epinephrine High-dose epinephrine 1st ACLS guideline (1974) Epinephrine in cardiac arrest PALS (1983) & NRP (1987) guidelines

18. High-Dose Epinephrine • High-dose epinephrine: 0.1 mg/kg (0.1 mL/kg 1:1000) • Animal studies shown to increase coronary and cerebral perfusion more than standard dose • Non-blinded trial in pediatric patients shown to improve survival and neurological outcomes • Well controlled adult and pediatric data failed to show an improvement in outcomes

19. PALS Guidelines • 2000 PALS guidelines • Standard-dose epinephrine is given and if no response is seen, repeat with either standard-dose OR high-dose epinephrine • 2005 PALS guidelines • No longer recommend the use of high-dose epinephrine in pediatric patients with pulseless arrest

20. Further Research • Survival rates post-cardiac arrest continue to be low • High-dose epinephrine and other adrenergic agents have not shown to improve survival and have many adverse effects • Increased myocardial oxygen consumption • Ventricular arrhythmias • Myocardial dysfunction

21. Timeline 1960 1970 1980 1990 2000 2010 Intracardiac epinephrine High-dose epinephrine 1st ACLS guideline (1974) Epinephrine in cardiac arrest Vasopressin research PALS (1983) & NRP (1987) guidelines

22. Vasopressin Use in Cardiac Arrest • Non-adrenergic agents are being further examined for use in cardiac arrest • High concentrations of endogenous vasopressin found in post-cardiac arrest patients • Increases in arterial and coronary pressures and myocardial and cerebral blood flow with vasopressin vs. standard-dose epinephrine

23. Vasopressin Pharmacology Klabunde RE. Cardiovascular Physiology Concepts. Lippincott Williams & Wilkins; 2005.

24. Vasopressin Use In Adults with Cardiac Arrest

25. Conclusions from Adult Vasopressin Studies • Adult trials comparing vasopressin and epinephrine failed to show differences in outcomes and survival • A possible benefit seen with vasopressin in patients with refractory cardiac arrest • More studies should be performed in order to better understand the role in refractory cardiac arrest

26. Advanced Cardiac Life Support (ACLS) American Heart Association. Management of Cardiac Arrest. Circulation 2005; 112: 167-187.

27. Vasopressin Dosing in Cardiac Arrest • Adult • 40 units IV once • ACLS recommends to replace either the first or second dose of epinephrine • Pediatric • No dosing recommendations exist

28. Beneficial Effects of Vasopressin in Prolonged Pediatric Cardiac Arrest: A Case Series Mann K et al. Resuscitation. 2002; 52: 149-156.

29. Case Series *Mean time between first and second doses of VP: 9.8 min (3-20 min) VP = vasopressin EPI = epinephrine Mann K et al. Resuscitation. 2002; 52: 149-156.

30. Timeline 1960 1970 1980 1990 2000 2010 Vasopressin pediatric case series (2004) Intracardiac epinephrine High-dose epinephrine 1st ACLS guideline (1974) Vasopressin animal research Epinephrine in cardiac arrest PALS (1983) & NRP (1987) guidelines Vasopressin adult studies & addition to ACLS guideline (2005)

31. Conclusions • Survival rates continue to be low in both in-hospital and out-of-hospital cardiac arrest • The ACLS guidelines state that vasopressin may be substituted for the first or second dose of epinephrine during pulseless arrest

32. Conclusions • Adult studies comparing vasopressin and epinephrine showed similar outcomes in ROSC and survival rates • Currently, the only pediatric vasopressin literature consists of a four patient case series which did show ROSC in a few patients

33. Conclusions • Epinephrine is still the drug of choice for the treatment of pulseless arrest in pediatric patients • More studies need to be done in order to characterize the use of vasopressin in the pediatric population

34. My Recommendations • Vasopressin could be considered in pediatric patients that fail to have ROSC after at least 2-3 doses of epinephrine • Dosing: 0.4 units/kg IV up to a max of 40 units, repeat dose once in 5-10 minutes if no ROSC • Epinephrine should continue to be given every 3-5 minutes after vasopressin is given if there is no ROSC

35. Current Research • A prospective, randomized, controlled trial of combination vasopressin and epinephrine to epinephrine only for in-intensive care unit pediatric cardiopulmonary resuscitation • Intervention: • Patient who do not respond to CPR and one standard-dose of epinephrine • Vasopressin 0.8 units/kg • Epinephrine 0.01 mg/kg (standard-dose)

36. Current Research • Inclusion • < 18 years • Cardiac arrest requiring chest compressions • Location of arrest in pediatric intensive care unit • No ROSC after one standard-dose of epinephrine • Exclusion • DNR orders • Patient not requiring chest compressions • Pregnancy

37. Current Research • Primary Outcome • Survival to hospital discharge • Secondary Outcomes • ROSC • Neurological outcomes • 24 hour survival rates

38. Current Research • Retrospective chart review (SLCH) • Patients between January 1, 2006 and June 30, 2010 who suffered from in-hospital cardiac arrest • Patients are excluded if the arrest occurred in the neonatal intensive care unit, operating room, and emergency room • Reviewing the usage of vasopressin as well as patient outcomes

39. Timeline 1960 1970 1980 1990 2000 2010 Vasopressin pediatric case series (2004) Intracardiac epinephrine RCT of vasopressin in pediatrics High-dose epinephrine 1st ACLS guideline (1974) Vasopressin animal research Epinephrine in cardiac arrest PALS (1983) & NRP (1987) guidelines Vasopressin adult studies & addition to ACLS guideline (2005) Addition of vasopressin to PALS?

40. Vasopressin Use in Pediatric cardiac arrest Brandy Bratcher, PharmD PGY2 Pharmacy Resident St. Louis Children’s Hospital Email: bnb2381@bjc.org Office: 314-454-6014