1. CALCIUM USE DURING IN-HOSPITAL PEDIATRIC
CARDIO PULMONARY RESUSCITATION:
A Report From the National Registry of Cardiopulmonary Resuscitation
Srinivasan V, Morris M C, Helfaer M. A, Berg R.A , Nadkarni V.M
Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia and
University of Pennsylvania, Philadelphia, Pennsylvania;
Department of Pediatrics, Morgan Stanley Children’s Hospital of New York-Presbyterian and
Columbia University Medical Center, New York, New York;
Department of Pediatrics, Steele Children’s Research Center, University of Arizona, Tucson,
Arizona
Pediatrics 2008;121;1144-1151

2. • The role of calcium administration during cardiopulmonary
resuscitation (CPR) remains controversial.
• Although calcium ions play a critical role in myocardial
contractile performance and impulse formation, limited
retrospective and prospective studies of calcium
administration during CPR have not shown any benefit.
• Furthermore, high serum calcium levels induced by
calcium administration may be detrimental. Several studies
have implicated cytoplasmic calcium accumulation in the
final common pathway of cell death.

3. • Calcium accumulation results from calcium’s entering cells after
ischemia and during reperfusion of ischemic organs; increased
cytoplasmic calcium concentration activates intracellular enzyme
systems, resulting in cellular necrosis.
• In 2000, the American Heart Association (AHA) published
guidelines limiting the recommended use of calcium to selected
resuscitation circumstances: documented hypocalcemia,
hyperkalemia, hypermagnesemia, and calcium channel blocker
overdose.
• These guidelines also explicitly stated that calcium should not be
used routinely to support circulation in the setting of cardiac arrest
(class III recommendation: not useful and may cause harm).

4. • The National Registry of Cardiopulmonary Resuscitation (NRCPR) is a
large, multicenter database that prospectively and rigorously
documents adult and pediatric in-hospital cardiac arrests.
• The authors conducted this study using the NRCPR database to
characterize patterns of calcium use during in-hospital pediatric CPR.
• They hypothesized that calcium continues to be used frequently during
in-hospital pediatric CPR and that its use varies by hospital-specific,
patient-specific, and event-specific characteristics.
• They also hypothesized that calcium use during in-hospital pediatric
CPR is associated with worse survival to hospital discharge, and worse
event survival and unfavorable neurologic outcome.

5. Methods
• Data were analyzed from 167 participating NRCPR hospitals that recorded
cardiopulmonary arrests of patients who were younger than 18 years and
provided 6 months of data.
• All patients who were younger than 18 years and experienced
cardiopulmonary arrest that required CPR at participating institutions
were eligible for this study.
• An event was defined as an arrest that required chest compressions
and/or defibrillation. An index event was defined as the patient’s first
cardiopulmonary arrest that required CPR during hospitalization. Only
index events were eligible for inclusion in the study.
• Out-of-hospital arrests, arrests that occurred in the delivery room or NICU,
arrests in patients with “do not attempt resuscitation” orders, and arrests
that were resolved by implantable defibrillator shocks were excluded.

6. • The prospectively selected primary outcome measure was survival to
hospital discharge.
• The secondary outcome measures included survival of event (defined as
return of spontaneous circulation for 20 minutes) and neurologic
outcome.
• The neurologic outcome was determined according to the pediatric
cerebral performance category (PCPC) scale as follows:
– (1) a normal neurologic state,
– (2) mild disability,
– (3) moderate disability,
– (4) severe disability,
– (5) coma or vegetative state, and
– (6) death.
• A favorable neurologic outcome was defined by a PCPC score of 1, 2, or 3
or no change from baseline PCPC scores

7. Statistics
• All statistical analyses were performed with a commercially
available statistical package (Stata 8, College Station, TX).
• Results are presented as means ± SD for variables that are
distributed normally.
• Variables that were not distributed normally are presented as
medians and interquartile ranges.
• Differences between groups were analyzed by the Wilcoxon rank-
sum test for continuous variables and the 2 test for dichotomous
variables

8. • Hospital, patient, and event variables associated with calcium use by
univariate analysis were included in stepwise multivariable logistic
regression analysis.
• All factors associated with primary and secondary outcomes on univariate
analysis were included in stepwise multivariable logistic regression to
describe the association of calcium use with outcome measures adjusted
for confounding factors.
• Odds ratios (ORs) with 95% confidence intervals (Cis) were reported. The
sample size was not planned.

9. RESULTS

10. • Calcium was provided during CPR significantly more often in
events that occurred in pediatric facilities (62% vs 35% in mixed
facilities vs 3% in adult facilities; and ICUs (77% vs 7% in
emergency departments).
• Cardiac illness (both surgical and medical) was significantly
associated with calcium use during CPR.
• A greater proportion of patients who subsequently received
calcium during CPR were on a vasoactive infusion at the time of
the arrest, compared with those who did not receive calcium (50%
vs 28%).

12. • In both groups, acute respiratory insufficiency and
hypotension were the most common immediate precipitating
causes of the arrest. Notably, preexisting major trauma and
acute airway obstruction were less likely to be associated
with calcium use during CPR.
• Of the 1477 events, 874 (59%) were pulseless throughout the
entire event, 274 (19%) became pulseless during the event,
and 329 (22%) had pulses throughout the event.
• Overall, more survivors than nonsurvivors underwent CPR for
15 minutes (54% vs 29%).

13. • The median duration of CPR was 30 minutes in the group that
received calcium, compared with 15 minutes in the group that did
not receive calcium.
• Similarly, the median number of epinephrine doses administered
was 4 in the group that received calcium compared with 2 in the
group that did not receive calcium.
• Loss of pulses during the event was more often associated with
calcium use, whereas presence of pulses throughout the event was
less likely to be associated with calcium use.
• Calcium use during CPR was significantly more likely when the first
documented pulseless rhythm was asystole; one third of children
who received calcium during CPR had asystole as the first
documented rhythm.

14. RESULT - ANALYSIS
• After controlling for confounding factors (ethnicity, facility type, event
location, illness category, preexisting conditions, interventions in place at
the time of the event, immediate precipitating causes, arrest rhythm,
concurrent advanced cardiac life support medications, and duration of
CPR for 15 minutes), calcium administration during CPR was
independently associated with poor survival to discharge and unfavorable
neurologic outcome after in-hospital pediatric CPR, as hypothesized.
• Twenty-one percent of patients survived to discharge when calcium was
used, compared with 44% who survived when calcium was not used (aOR:
0.6; 95% CI: 0.5– 0.9).
• In addition, only 15% of patients had favorable neurologic outcome when
calcium was administered during CPR, compared with 35% with favorable
neurologic outcome when calcium was not administered

16. • The authors also examined calcium use during CPR in specific
circumstances of interest in which administration of calcium might be
indicated.
• First, in the settings of metabolic electrolyte abnormalities and toxicologic
abnormalities, calcium use during CPR was not associated with worse
event survival or survival to discharge after adjustment for confounding
factors.
• Second, in the population of postcardiac surgical infants, after adjustment
for confounding factors, the use of calcium during CPR was associated
with worse event survival; however, in this setting, calcium use during CPR
was not significantly associated with reduced survival to hospital discharge
or unfavorable neurologic outcome.

17. • After we excluded patients in the settings of metabolic/electrolyte
abnormalities, toxicologic abnormalities, and postcardiac surgical infants,
calcium use during CPR (n = 898) continued to be associated with worse
survival to discharge and was not associated with favorable neurologic
outcome after adjustment for potentially confounding variables.

18. DISCUSSION
• This report of in-hospital pediatric cardiopulmonary arrests in 1477
consecutive children documents calcium administration during
resuscitation of 659 (45%) children.
• This study shows that calcium use during CPR is strongly influenced by
hospital-specific, patient-specific, and arrest-specific characteristics.
• Previous studies of adults had speculated that calcium administration
during CPR might benefit a subset of patients with asystole and pulseless
electrical activity; however, subsequent limited prospective and
retrospective adult studies of calcium administration during resuscitation
in these settings failed to demonstrate any benefit.

19. • Later studies that consisted of large prospective cohorts of adults who
sustained both in-hospital and out-of-hospital cardiac arrests did not show
any association between the use of standard advanced cardiac life support
medications (including calcium) and survival.
• On the basis of these data, the AHA 2000 guidelines recommended
limiting the use of calcium to select resuscitation circumstances.
• Specific indications for calcium use during CPR (hyperkalemia,
documented hypocalcemia, hypermagnesemia, and calcium channel
blocker overdose) are captured in the NRCPR under the categories of
metabolic/ electrolyte abnormalities and toxicologic abnormalities.

20. • This study revealed that calcium was administered to 45% of children
who were treated with CPR.
• The combined incidence of metabolic/electrolyte and toxicologic
abnormalities (as both preexisting conditions and immediate
precipitating causes) in the NRCPR database is only 25%.
• Also, calcium was administered in asystole (49%) and pulseless
electrical activity (42%). This suggests that calcium is often used in
circumstances other than those recommended by the pediatric
advanced life support guidelines.

21. • There are several reasons that calcium might be used so frequently during
CPR in children. In neonates and infants, the immature myocardium
depends more on extracellular calcium levels because intracellular calcium
stores are limited. This age group has significant risk factors such as
cardiac bypass surgery, sepsis, and prematurity that have a significant
impact on myocardial function and extracellular ionized calcium
concentrations. Perhaps in part because of these factors, practitioners
chose to provide calcium in 44% of events involving neonates and infants
in this study. Nevertheless, in this age category, those who received
calcium during CPR had worse survival to discharge (26%) compared with
those who did not (55%).

22. • Specifically, in the population of postcardiac surgical infants, after
adjustment for confounding factors, the use of calcium during CPR was
associated with worse event survival; however, calcium use during CPR
was not significantly associated with reduced survival to hospital discharge
or unfavorable neurologic outcome.
• The frequent use of calcium during CPR in other age and diagnostic
categories may reflect medical futility and a “last-ditch” attempt to try all
possible therapies during resuscitation.
• Irrespective of event duration, calcium use during CPR was associated with
worse survival to discharge and unfavorable neurologic outcome. This
finding has important implications because of the widely known role of
calcium in mediating reperfusion injury in the setting of ischemia resulting
in cell death.

23. LIMITATIONS
• An important limitation of the study results from the lack of explicit
documentation of specific indications for calcium use and details of
calcium dosing during CPR as captured in the NRCPR. A dose-response
effect, if observed, could have provided stronger evidence for the effect of
calcium administration on outcome.
• Another important limitation is the inability to adjust for variation in
facility characteristics and physician and nurse staffing in different
settings, resulting in our inability to use hierarchical cluster modeling.

24. CONCLUSION
• This study has important implications. First, the results emphasize that
calcium continues to be used frequently during in-hospital pediatric CPR,
despite guidelines that recommend limiting the use of calcium to specific
circumstances. Pediatric advanced life support guidelines published by the
AHA in 2005 continue to restrict the use of calcium to specific
circumstances, including hyperkalemia, documented hypocalcemia,
hypermagnesemia, and calcium channel blocker overdose.
• Second, the use of calcium during CPR without such indications is
associated with worse survival to discharge and unfavorable neurologic
outcome, perhaps because of reperfusion injury to the ischemic brain,
heart, and other organs mediated by calcium.
THANK YOU………..