Vasopressin_Use_in_Pediatric_cardiac_arrest_(GPPG

Report
Brandy Bratcher, PharmD
PGY2 Pharmacy Resident
St. Louis Children’s Hospital




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


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.


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.


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.
Category
Score
Clinical Features
Normal
1
-School age child attends regular school classroom at age appropriate level
Mild disability
2
-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 disability
4
-Dependent on others for daily support because of impaired brain function
Coma or vegetative
state
5
Brain death
6
-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
-Apnea, areflexia, or EEG silence
Fisher DH. Assessing the outcome of pediatric intensive care. J Pediatr. 1992; 121: 68-74.





Environment where arrest occurs
Pre-existing conditions
Duration of pulseless arrest without CPR
Initial electrocardiographic (EKG) rhythm
Quality of advanced life support interventions

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

Respiratory failure (most common)

Cardiac insufficiency

Miscellaneous


Upper airway obstruction
Restrictive airway disease




Asthma
Cystic fibrosis (CF)
Bronchopulmonary dysplasia (BPD)
Impaired air exchange


Pneumonia
Surfactant deficiency

Congenital Heart Disease

Coronary Arterial Disease

Myocardial Disease

Conduction System Abnormality/Arrhythmia

Electrolyte disturbances








Hyperkalemia, hypokalemia, hypomagnesemia
Pulmonary hypertension
Inborn errors of metabolism
Sudden infant death syndrome (SIDS)
Hypothermia
Commotio cordis
Non-accidental trauma
Poisoning

Pre-arrest (Protect)


No flow (Preserve)


Initiate CPR and defibrillation (if indicated)
Low flow (Resuscitate)



Early recognition of respiratory failure and/or shock to
prevent cardiac arrest
Utilize effective CPR techniques
Administer medication therapy as indicated by PALS
Post-Resuscitation (Regenerate)


Optimize cardiac output and perfusion
Treat underlying conditions

Advanced Cardiac Life Support (ACLS)

Pediatric Advanced Life Support (PALS)

Neonatal Resuscitation Program (NRP)
1960
1970
Intracardiac
epinephrine
Epinephrine
in cardiac
arrest
1980
1990
1st ACLS
guideline
(1974)
PALS (1983) &
NRP (1987)
guidelines
2000
2010
American Heart Association. Management of Cardiac Arrest. Circulation 2005; 112: 167-187.
1960
1970
Intracardiac
epinephrine
Epinephrine
in cardiac
arrest
1980
1st ACLS
guideline
(1974)
1990
High-dose
epinephrine
PALS (1983) &
NRP (1987)
guidelines
2000
2010




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

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

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
1960
1970
Intracardiac
epinephrine
Epinephrine
in cardiac
arrest
1980
1st ACLS
guideline
(1974)
1990
2000
High-dose
epinephrine
PALS (1983) &
NRP (1987)
guidelines
Vasopressin
research
2010

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
Klabunde RE. Cardiovascular Physiology Concepts. Lippincott Williams & Wilkins; 2005.



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
American Heart Association. Management of Cardiac Arrest. Circulation 2005; 112: 167-187.

Adult

40 units IV once
 ACLS recommends to replace either the first or second
dose of epinephrine

Pediatric

No dosing recommendations exist
Mann K et al. Resuscitation. 2002; 52: 149-156.
7 months
2
3
18 months
3 months
5 years
5
3
4
0.4 units/kg
0.4 units/kg
0.4 units/kg
# of EPI doses prior
to VP
VP dose
3
# of VP doses
1
2
2
2
2
2
Time from 1st VP to
ROSC (min)
Time from 2nd VP to
ROSC (min)
ROSC (> 24 hrs)
2
5
-
-
23
6
-
2
-
-
3
1
N
N
N
N
Y
Y
Discharge
-
-
-
-
N
Y
0.4 units/kg
*Mean time between first and second doses of VP: 9.8 min (3-20 min)
Mann K et al. Resuscitation. 2002; 52: 149-156.
VP = vasopressin
EPI = epinephrine
1960
1970
Intracardiac
epinephrine
Epinephrine
in cardiac
arrest
1980
1990
2000
2010
Vasopressin
pediatric
High-dose
1st ACLS
case series
epinephrine
guideline
Vasopressin (2004)
(1974)
animal
research
PALS (1983) &
Vasopressin
NRP (1987)
adult studies
guidelines
& addition to
ACLS guideline
(2005)


Survival rates continue to be low in both inhospital 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


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


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



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


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)

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

Primary Outcome


Survival to hospital discharge
Secondary Outcomes



ROSC
Neurological outcomes
24 hour survival rates

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

1960
1970
Intracardiac
epinephrine
Epinephrine
in cardiac
arrest
1980
1990
2000
2010
Vasopressin
RCT of
pediatric
High-dose
vasopressin
1st ACLS
case series
epinephrine
in pediatrics
guideline
Vasopressin (2004)
(1974)
animal
research
PALS (1983) &
Vasopressin
NRP (1987)
Addition of
adult studies
guidelines
vasopressin
& addition to
to PALS?
ACLS guideline
(2005)
Brandy Bratcher, PharmD
PGY2 Pharmacy Resident
St. Louis Children’s Hospital
Email: bnb2381@bjc.org
Office: 314-454-6014

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