1. 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 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.  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.  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. CategoryScoreClinical Features Normal1-School age child attends regular school classroom at age appropriate level Mild disability2-Conscious, alert, and able to interact at an age appropriate level -Attends school but grade perhaps not appropriate for age -May have mild neurologic deficit Moderate disability 3-Sufficient cerebral function for independent activities of daily living -School age child attends special education classroom -May have learning deficit Severe disability4-Dependent on others for daily support because of impaired brain function Coma or vegetative state 5-Any degree of coma without brain death -Unawareness even if awake in appearance -No interaction with environment -Cerebral unresponsiveness -No evidence of cortical function and not aroused by verbal stimuli -May have spontaneous eye movement and sleep/wake cycles Brain death6-Apnea, areflexia, or EEG silence Fisher DH. Assessing the outcome of pediatric intensive care. J Pediatr. 1992; 121: 68-74.

7.  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

9.  Respiratory failure (most common)  Cardiac insufficiency  Miscellaneous

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

11.  Congenital Heart Disease  Coronary Arterial Disease  Myocardial Disease  Conduction System Abnormality/Arrhythmia

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

13.  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. AAdvanced Cardiac Life Support (ACLS) PPediatric Advanced Life Support (PALS) NNeonatal Resuscitation Program (NRP)

15. 196019701980199020002010 Intracardiac epinephrine Epinephrine in cardiac arrest 1 st ACLS guideline (1974) PALS (1983) & NRP (1987) guidelines

16. American Heart Association. Management of Cardiac Arrest. Circulation 2005; 112: 167-187.

17. 196019701980199020002010 Intracardiac epinephrine Epinephrine in cardiac arrest 1 st ACLS guideline (1974) PALS (1983) & NRP (1987) guidelines High-dose epinephrine

18.  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.  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.  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. 196019701980199020002010 Intracardiac epinephrine Epinephrine in cardiac arrest 1 st ACLS guideline (1974) PALS (1983) & NRP (1987) guidelines High-dose epinephrine Vasopressin research

22.  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. Klabunde RE. Cardiovascular Physiology Concepts. Lippincott Williams & Wilkins; 2005.

25.  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. American Heart Association. Management of Cardiac Arrest. Circulation 2005; 112: 167-187.

27.  Adult  40 units IV once  ACLS recommends to replace either the first or second dose of epinephrine  Pediatric  No dosing recommendations exist

28. Mann K et al. Resuscitation. 2002; 52: 149-156.

29. 7 months18 months3 months5 years # of EPI doses prior to VP 323534 VP dose0.4 units/kg # of VP doses122222 Time from 1 st VP to ROSC (min) 25--236 Time from 2 nd VP to ROSC (min) -2--31 ROSC (> 24 hrs)NNNNYY Discharge----NY *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. 196019701980199020002010 Intracardiac epinephrine Epinephrine in cardiac arrest 1 st ACLS guideline (1974) PALS (1983) & NRP (1987) guidelines High-dose epinephrine Vasopressin animal research Vasopressin adult studies & addition to ACLS guideline (2005) Vasopressin pediatric case series (2004)

31.  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.  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.  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.  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.  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.  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.  Primary Outcome  Survival to hospital discharge  Secondary Outcomes  ROSC  Neurological outcomes  24 hour survival rates

38.  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. 196019701980199020002010 Intracardiac epinephrine Epinephrine in cardiac arrest 1 st ACLS guideline (1974) PALS (1983) & NRP (1987) guidelines High-dose epinephrine Vasopressin animal research Vasopressin adult studies & addition to ACLS guideline (2005) Vasopressin pediatric case series (2004) RCT of vasopressin in pediatrics Addition of vasopressin to PALS?

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