PPA News

Posted by: Brandy Zeller on Jan 18, 2016

Written by: Bethany A. Wattles, PharmD PGY2 Critical Care Pharmacy Resident Kosair Children’s Hospital – Louisville, KY

In 2015, the American Heart Association (AHA) provided an update to the Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care including an update to Pediatric Advanced Life Support (PALS)1 recommendations. Outcomes have improved for pediatric in-hospital cardiac arrest (IHCA) as evidenced by the increase in rates of return of spontaneous circulation (ROSC) from 39% to 77% and increased survival to hospital discharge from 24% to 43%1. However, rates of survival from out-of-hospital cardiac arrest (OHCA) have not seen significant improvement over the past 5 years.

The following is a review of the 2015 update to the PALS guidelines with a focus on medication therapy and supporting literature published since release of the 2010 guidelines. This review does not address updates to BLS and Neonatal Resuscitation, which are discussed in Parts 11 & 13 of the 2015 AHA guidelines.

Atropine for Premedication During Emergency Intubation

Bradycardia is a known sequelae of emergency pediatric intubation. Potential mechanisms for bradycardia include hypoxia/ischemia, vagal response, reflex to positive pressure ventilation, or a side effect of pharmacologic agents such as succinylcholine or fentanyl. Atropine has been used historically to prevent reflex bradycardia caused by vagal stimulation, but studies have failed to support its routine use for this indication. Jones et al. 2 conducted a prospective, multi-center observational study of 264 children in France receiving atropine prior to non-planned intubations. Although atropine was found to have a significant effect on heart rate in both neonates and children, it was associated with an overall lower intensive care unit (ICU) mortality in children only, suggesting an effect independent of bradycardia. Jones et al.3 also conducted a study of 322 intubations in children receiving atropine and found that atropine significantly reduced the prevalence of new arrhythmias during intubation and did not result in conduction disturbances. Both found that atropine at preintubation doses of 0.02 mg/kg was effective, without a minimum dose requirement (as mentioned in past Guidelines).

The 2015 recommendations suggest that atropine can be considered in specific situations but fail to mention specific at-risk populations such as infants or patients who are experiencing baseline bradycardia prior to intubation.

2015 Recommendations – New

The available evidence does not support the routine use of atropine preintubation of critically ill infants and children. It may be reasonable for practitioners to use atropine as a premedication in specific emergency intubations when there is higher risk of bradycardia (eg, when giving succinylcholine as a neuromuscular blocker to facilitate intubation) (Class IIb, LOE C-LD). A dose of 0.02 mg/kg of atropine with no minimum dose may be considered when atropine is used as a premedication for emergency intubation (Class IIb, LOE C-LD). This new recommendation applies only to the use of atropine as a premedication for infants and children during emergency intubation.

Vasopressors During Cardiac Arrest

Vasopressors have been used during cardiac arrest in both pediatric and adult patients to restore spontaneous circulation by optimizing coronary perfusion. When used for this indication vasopressors also have the potential to cause harmful effects due to vasoconstriction and increased myocardial oxygen consumption. Despite historical use, there is a lack of literature to support use of any vasopressors in pediatric cardiac arrest.

Enright et al. 4 conducted a prospective, observational study in 9 pediatric patients experiencing primary OHCA. Three of the four patients who received epinephrine experienced mortality, which authors suggested could be attributable to catecholamine-sensitive cardiac disorders that led to cardiac arrest. When referencing this study, the guidelines state that there are too many confounders to draw conclusions regarding vasopressor therapy. In 2011 Jacobs et al.5 evaluated the effect of epinephrine on survival in OHCA in adult patients. This double blind randomized placebo-controlled trial included 534 patients and found that epinephrine significantly improved the likelihood of achieving ROSC but did not lead to improvements in survival to hospital discharge.

More recently, Andersen et al.6 conducted a retrospective analysis of the time to epinephrine administration in 1558 pediatric patients with an in-hospital cardiac arrest and an initial nonshockable rhythm. They found that a delay in epinephrine administration was associated with a decreased chance of survival to hospital discharge, ROSC, 24-hour survival and survival with favorable neurological outcome. It is important to note that these recommendations were not included in the most recent 2015 guidelines.

An overall lack of literature regarding vasopressor therapy in pediatric cardiac arrest prevents guidelines from providing a strong recommendation. Ethical considerations will likely prevent ideally-designed clinical trials from being undertaken in the future. However, retrospective studies with a focus on site of cardiac arrest and initial rhythm could provide valuable information for future guidelines.

2015 Recommendations – New

It is reasonable to administer epinephrine in pediatric cardiac arrest (Class IIa, LOE C-LD).

Amiodarone and Lidocaine for Shock-Refractory Ventricular Fibrillation (VF) and Pulseless Ventricular Tachycardia (pVT)

Previous PALS guidelines recommended amiodarone as initial therapy for VF or pVT based on pediatric case series and extrapolation from adult studies. Valdes et al. 7 conducted a retrospective cohort study in 889 pediatric patients with pVT/VF and found lidocaine to be independently associated with improved ROSC and 24-hour survival. However, they found amiodarone was not found to be superior. Neither agent was found to be associated with an increased survival to hospital discharge.

2015 Recommendations – New

For shock-refractory VF or pVT, either amiodarone or lidocaine may be used (Class IIb, LOE C-LD).

Post-Cardiac Arrest Fluids and Inotropes

Although myocardial dysfunction and vascular instability are known complications after resuscitation from cardiac arrest, previous guidelines did not provide recommendations for maintaining blood pressure post-cardiac arrest.

Topjian and colleagues8 evaluated post-cardiac arrest blood pressures in 383 pediatric patients and found that a systolic blood pressure less than the fifth percentile for age and sex within the first 6 hours following ROSC was associated with a higher rate of in-hospital mortality and worse neurological outcomes. Lin et al.9 evaluated the clinical features of 228 children in the first hour after achieving ROSC and found that a normal heart rate, blood pressure, and adequate urine output were positive predictors of survival to hospital discharge. Similarly, in 2013, Lin et al. 10 conducted a multi-center prospective study in 362 children after traumatic OHCA. They concluded that normal heart rate, blood pressure and urine output, as well as sinus rhythm, Glasgow Coma Scale of greater than 7 and noncyanotic skin color, were predictors of survival.

2015 Recommendations – New

After ROSC, we recommend that parenteral fluids and/or inotropes or vasoactive drugs be used to maintain a systolic blood pressure greater than fifth percentile for age (Class I, LOE C-LD). When appropriate resources are available, continuous arterial pressure monitoring is recommended to identify and treat hypotension (Class I, LOE C-EO).


  1. de Caen AR, et al. Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(18 Suppl 2):S526-42.
  2. Jones, P et al. Atropine for critical care intubation in a cohort of 264 children and reduced mortality unrelated to effects on bradycardia. PLoS One. 2013;8(2):e57478.
  3. Jones P, et al. The effect of atropine on rhythm and conduction disturbances during 322 critical care intubations. Pediatr Crit Care Med. 2013;14(6):e289-97.
  4. Enright K, et al. Primary cardiac arrest following sport or exertion in children presenting to an emergency department: chest compressions and early defibrillation can save lives, but is intravenous epinephrine always appropriate? Pediatr Emerg Care. 2012;28(4):336-9.
  5. Jacobs IG, et al. Effect of adrenaline on survival in out-of-hospital cardiac arrest: a randomized double-blind placebo-controlled trial. Resuscitation. 2011;82:1138-1143.
  6. Andersen LW, et al. Time to Epinephrine and Survival After Pediatric In-Hospital Cardiac Arrest. JAMA. 2015;314(8):802-10.
  7. Valdes SO, et al. Outcomes associated with amiodarone and lidocaine in the treatment of in-hospital pediatric cardiac arrest with pulseless ventricular tachycardia or ventricular fibrillation. Resuscitation. 2014;85(3):381-6.
  8. Topijan AA, et al. Early postresuscitation hypotension is associated with increased mortality following pediatric cardiac arrest. Crit Care Med. 2014;42(6):1518-23.
  9. Lin YR, et al. Post-resuscitative clinical features in the first hour after achieving sustained ROSC predict the duration of survival in children with non-traumatic out-of-hospital cardiac arrest. Resuscitation. 2010;81(4):410-7.
  10. Lin YR, et al. Predictors of survival and neurologic outcomes in children with traumatic out-of-hospital cardiac arrest during the early postresuscitative period. J Trauma Acute Care Surg. 2013;75(3):439-47.