High-Dose Epinephrine in Pediatric Out-of-Hospital Cardiopulmonary Arrest

(1)

High-Dose

Epinephrine

in

Pediatric

Out-of-Hospital

Cardiopulmonary

Arrest

Ronald A. Dieckmann, MD, MPH; and Ralph Vardis, MD

ABSTRACT. Objective. To compare the efficacy of

high-dose epinephrine (HDE) and standard-dose

epi-nephrine (SDE) for out-of-hospital treatment of pediatric cardiopulmonary arrest (CPA).

Design. Forty-eight-month retrospective cohort study.

Setting. Prehospital emergency medical services (EMS) system of a large metropolitan region.

Patients. All children younger than 18 years of age, who suffered nontraumatic CPA, did not meet local EMS criteria for death in the field, and were treated by para-medics according to EMS pediatric CPA protocols.

Interventions. Paramedics administered HDE (>0.1 mg/

kg), SDE (<0.1 mg/kg), or no epinephrine (NE), based on base hospital physician order and availability of access for drug delivery. Protocols permitted either HDE or SDE. The drug was given through an endotracheal tube, intraosseous line, or intravenous line.

Main outcome measures. Return of spontaneous circu-lation (ROSC) and return of an organized electrical rhythm (ROER) in the ambulance and emergency depart-ment, hospital admission, hospital discharge, and short-and long-term neurologic outcome by pediatric cerebral performance category (PCPC) score.

Results. During the study period, 65 children met in-clusion criteria and underwent attempted out-of-hospital resuscitation. Forty patients (62%) received HDE (mean dose ± SD, 0.19 ± 0.06 mg/kg); 13 patients (20%) received

SDE (mean dose ± SD, 0.02 ± 0.02 mg/kg); and 12

pa-tients (18%) received NE. The HDE and SDE groups were statistically different only in epinephrine dose but not in age, gender, proportion of asystolic presenting rhythms, success of endotracheal tube intubation or intraosseous line insertion, rate of ROSC, rate of ROER, survival, or proportion of sudden infant death syndrome final diag-noses. Fifty-four children (83%) presented in asystole, 5 (8%) had pulseless electrical activity (PEA), and 6 (9%) had ventricular fibrillation (VF). None presented with either supraventricular tachycardia or ventricular tachy-cardia. Thirty-nine patients receiving HDE had asystole

or VF as presenting rhythms, 4 (10%) had ROER, and 1

had ROSC. The single child receiving HDE presenting with PEA did not have ROSC. Ten patients receiving

SDE had asystole or VF, 2 (20%) had ROER, and none

had ROSC. There were 3 children receiving SDE who

had PEA, and 1 had ROSC. Eleven patients receiving NE

From the Department of Eniergency Services, San Francisco General

Hospital, and the Department of Pediatrics, University of California, San

Francisco.

Presented at the International Conference Ofl Pediatric Resuscitation,

Amer-ican Academy of Pediatrics, and the American Heart Association, Wash-ington DC, June 10-12, 1994.

Received for publication Oct 14, 1994; accepted Feb 1, 1995.

Reprint requests to (R.A.D.) 1 E21 , Emergency Department, San Francisco

General Hospital, 11)01 Potrero Ave. San Francisco, CA 94110.

Acad-emy of Pediatrics.

had asystole or VF, and none had ROER. One child

receiving NE had PEA and ROSC. Altogether, 1 patient receiving HDE, 1 receiving SDE, and 1 receiving NE had ROSC in the field, which continued in the emergency

department; all 3 were admitted to the hospital. Two

children (3%), 1 receiving HDE and 1 receiving SDE,

survived to hospital discharge. The survivor receiving HDE had spastic quadriplegia and profound neurologic handicaps at discharge, with a PCPC score of 4 (severe disability with daily living milestones below the 10th percentile and excessive dependence on others for provi-sion of activities of daily living); at a 1-year follow-up, she had a PCPC score of 4. The survivor receiving SDE was neurologically healthy at discharge; at discharge and

at follow-up at age 1 year, she had a PCPC score of 1

(age-appropriate level of functioning and developmen-tally appropriate).

Conclusions. HDE does not seem to improve the rates

of ROER and ROSC, hospital admission, survival, or

neurologic outcome when compared with SDE for treat-ment of out-of-hospital pediatric CPA. A large, blinded prospective clinical trial testing different epinephrine doses is necessary to determine drug efficacy and safety. Future pediatric CPA studies must standardize reporting of core data elements, using the adult Utstein criteria modified for pediatrics, to allow valid treatment compar-isons. Overall, survival in out-of-hospital pediatric CPA is dismal. When strict inclusion criteria for cardiac stand-still are observed, outcome from out-of-hospital pediatric

CPA may be significantly worse than previously

re-ported. Like adults, children failing out-of-hospital ad-vanced life support are extremely unlikely to have mean-ingful survival. Out-of-hospital pediatric treatment and

transport policies should assure delivery of appropriate advanced life support; in some well-controlled situa-tions, termination of resuscitation without hospital trans-port may be possible. Immediate grief counseling for the parents and critical incident stress debriefing for ambu-lance personnel are essential. Pediatrics 199595:901-913;

pediatric cardiopulmonary arrest, pediatric

cardiopulmo-nary resuscitation, epinephrine.

ABBREVIATIONS. CPA, cardiopulmonary arrest; ED, emergency department; AHA, American Heart Association; HDE, high-dose epinephrine; SDE, standard-dose epinephrine; PEA, pulseless electrical activity; SVT, supraventricular tachycardia; VT, ventric-ular tachycardia; VF, ventricular fibrillation; ALS, advanced life support; 10, intraosseous; IV, intravenous; EMS, emergency

med-ical services; ET, endotracheal; NE, no epinephrine; ROER, return

of an organized electrical rhythm; ROSC, return of spontaneous

circulation; PCPC, pediatric cerebral performance category; SIDS,

sudden infant death syndrome.

Outcome from pediatric cardiopulmonary arrest

(CPA) in either in-hospital or out-of-hospital settings is poor.1’1 Out-of-hospital survival may be even less

at Viet Nam:AAP Sponsored on September 1, 2020

www.aappublications.org/news

(2)

902 HIGH-DOSE EPINEPHRINE

than what has been documented to date, because of

technical limitations in field measurement of

low-perfusion states, variable and ambiguous definitions

of CPA, and unreliability and inconsistency in

re-porting of core patient data. Also, investigators to

date have not clearly distinguished between

pediat-nc CPA in the emergency department (ED) or

in-hospital setting versus CPA in the out-of-hospital

setting-where there are often multiple features in

the patients’ presentations and treatment

environ-ments that may substantially decrease probability of

survival.

The American Heart Association (AHA) has

pro-mulgated national guidelines for pharmacologic

treatment of pediatric CPA, most recently in 1992.12

In AHA guidelines and in all national

recommenda-tions on pediatric resuscitation, epinephrine is the

mainstay of drug treatment.1’7 When administered

experimentally during cardiac standstill, its a-ago-nistic properties are associated with increased aortic

diastolic pressure, improved coronary artery

perfu-sion, enhanced cardiac performance, and heightened survival.182#{176} In children, however, there is surpris-ingly little scientific foundation for use of

epineph-rine in CPA. Guidelines are largely based on adult

studies, animal experimentation, and anecdotal

re-ports.

In the absence of substantive scientific data on

the optimal dose of epinephrine, the 1980 and 1986

AHA guidelines recommended a uniform

epi-nephrine dose of 0.01 mg/kg for all doses in

pedi-atric CPA.21’22 In 1991, however, an influential

study concluded that high-dose epinephrine

(HDE) would dramatically improve survival in

childhood CPA, when compared to standard-dose

epinephrine (SDE)23’24; this in-hospital report

re-mains the only pediatric data on the purported

benefits of HDE, although most reported pediatric

CPAs have occurred out of hospital.25 Meanwhile,

recent studies of HDE in adult CPA have shown

little benefit in any setting.2629

With a small amount of animal data, a few

anec-dotal reports, and a controversial human study of

HDE in children, the AHA modified their 1992

re-suscitation guidelines and listed HDE as a class lib

intervention for pediatric CPA (not well established

by evidence, maybe helpful, and probably not

harm-ful). The new epinephrine dose recommendation

provided for an initial SDE dose of 10 pg/kg (0.01

mg/kg) and a subsequent HDE dose of 100 pg/kg

(0.1 mg/kg).12

We compared the effects of SDE and HDE on

survival from out-of-hospital pediatric CPA over a

4-year period. This report is the first out-of-hospital

study of SDE and HDE. It is only the second

pub-lished analysis of SDE versus HDE but contrasts

markedly with the conclusions of the previous

inves-tigator. We also examined key prognostic features of

CPA presentations and success of and response to

field and ED interventions vis-a-vis patient

cardio-vascular and short- and long-term neurologic

out-comes.

METHODS

The study population included all atraumatic children younger than I 8 years of age, who presented in the out-of-hospital setting unresponsive, pulselesss, and apneic and met inclusion criteria

(Table 1). This included children whose initial heart rhythm was either asystole, pulseless electrical activity (PEA), pulseless su-praventricular tachycardia (SVT), pulseless ventricular

tachycar-dia (VT), or ventricular fibrillation (VF).

Paramedics followed prehospital advanced life support (ALS) resuscitation protocols for pediatric bradyasystolic arrest (Fig I A) or for pediatric VF and pulseless VT (Fig IB). Trauma patients with CPA were excluded from the study group, because the trauma CPA protocol did not include epinephrine administration.

The treatment protocols stipulated that the paramedics perform electrical defibrillation and/or endotracheal intubation, then at-tempt vascular access using the following procedure; they first tried to insert an intraosseous (10) needle into the proximal tibia using a standard technique. If the 10 insertion failed, they at-tempted intravenous (IV) cannulation. If the child was older than 5 years of age, only an IV cannulation was attempted.

After initial patient assessment, defibrillation, and/or intuba-tion, and 10 line attempt, the paramedic then established radio or

telephone contact with the Paramedic Base Hospital at San Fran-cisco General Hospital, where the base hospital physician ordered drugs and doses. The written resuscitation protocols specifically suggest the lower SDE, because in 1989 the San Francisco Emer-gency Medical Services (EMS) Agency would not allow routine

HDE administration or randomization of SDE and HDE in chil-dren. But base hospital physicians were permitted by protocol to order a higher epinephrine dose, which could be immediately

taken from a conspicuous radio room wall chart giving both SDE and HDE doses by estimated patient weight. Parental informed consent for a child to receive HDE was not deemed necessary by

the San Francisco EMS Agency or the California EMS Authority. Paramedics approximated the child’s weight based on informa-tion from the care giver or visual estimation, then drew up the requested dose of epinephrine into a disposable 1-, 3-, or 6-mL syringe. Epinephrine was administered by the IV, 10, or

endotra-cheal (ET) routes, using either HDE (0.1 to 0.2 mg/kg), or SDE (0.01 mg/kg), through the first available delivery route. If neither

10 nor IV access was immediately established, the drug was administered ET. Several children received no epinephrine (NE) in

the field, because paramedics were unable to successfully insert an

ET tube or establish vascular access.

For ET epinephrine administration, a blunt-tipped 5-F feeding

tube was attached to a syringe and passed beyond the distal end of the tube. Epinephrine, either the 1:1000 or 1:10000 solution

diluted to a total volume of 0.5 mL/kg, was injected directly into

the trachea. Three to five lung inflations were performed to dis-perse the drug distally.

The Paramedic Base Hospital at San Francisco General Hospital was contacted by radio or telephone on every study patient. Data were recorded by the mobile intensive care nurses on the Base Hospital Record. All San Francisco ambulance personnel at the time of the study were trained to a paramedic level and certified in both pediatric endotracheal intubation and 10 line placement by the San Francisco EMS Agency.

Study data were collected from the Paramedic Base Hospital

TABLE 1. Pediatric Out-of-Hospital Cardiopulmonary Arrest Study Inclusion Criteria

1.Age <18 years 2. Apnea, unresponsiveness

3. No detectable central pulse or blood pressure 4. NONE of the following Death-in-the-Field criteria:

Rigor mortis with documented asystole Decapitation

Total incineration Decomposition

Apnea and separation from the body of either the heart, the liver, or the brain

Mass casualty circumstances where triage principles preclude cardiopulmonary resuscitation on every patient

Whenever the base hospital physician, in consultation with

the scene paramedic, believes that resuscitation is hopeless

(3)

B

.Atth. dlscrstlon of the Baa. Hoepftal Physician, substantially hlh.r doses of .pinephrin. may be ordered andgiven.

Atthe dIscretion ofthe Base Hospataf Physectan. substanffaily higher doses

of epfneghrtne may be ordered an#{248}given.

Fig 1. Prehospital ALS resuscitation protocols for pediatric bradyasystolic arrest (A) or pediatric VF and pulseless VT (B). Pediatric Prehospital Treatment Protocols, San Francisco Emergency Medical Services Agency, San Francisco Department of Public Health, 1989.

records, the paramedic run records, the ED charts, the hospital charts, and the coroner’s records for 48 months, from September

15, 1989, to September 14, 1993. Survivors’ hospital discharge

records and follow-up ambulatory records were evaluated for neurologic status. Recorded for each patient were: type of CPA (medical or trauma); age; gender; weight (obtained from both the field estimates and medical records for all survivors or from the coroner’s report for nonsurvivors); initial cardiac rhythm and heart rate; field El, 10, or IV success or failure; electrical counter-shock; epinephrine dose(s) per kilogram of child’s body weight; route(s) of epinephrine administration; other resuscitative medi-cations by kilogram of body weight and route of delivery; return of an organized electrical rhythm (ROER); and return of sponta-neous circulation (ROSC); ED presentation; ED ALS interventions and response; hospital admission; survival to hospital discharge;

final hospital or coroner’s diagnosis; and survivors’ short- and

long-term neurologic status.

Whether the CPA was witnessed or unwitnessed and preinter-vention time intervals (eg, time to bystander CPR, time to endo-tracheal intubation, and time to first epinephrine dose) were in-consistently and unreliably reported and therefore were not entered into the database. An exact out-of-hospital and ED epi-nephrine dose was established for each child based on the true body weight obtained in the hospital or by the coroner, not from the paramedic’s field weight estimations. ROSC was defined as presence of a palpable pulse or detectable blood pressure. ROER, defined as conversion from asystole or VF to any organized elec-trical rhythm (sinus, PEA, SVT, or VT), was regarded as an inter-mediate measure of drug response, because of the known unreli-ability of blood pressure assessment in the field for children younger than 6 years of age3#{176}and the possibility of low but unmeasureable perfusion in these children. Hospital admission was defined as admission to a hospital ward for at least I hour. Survival was defined as survival to hospital discharge.

Standard-ized short- and long-term neurologic assessments were conducted for survivors, using a recently described Pediatric Cerebral Per-formance Category (PCPC) score.3

Successful El placement was determined by the ED physician or coroner. 10 placement was confirmed by either paramedic instillation of drugs and fluids without resistance or by the ED

physician and/or coroner’s report.

Statistical Analysis

Fisher’s exact test was used for analysis of categorical data, and the Mann-Whitney test was used for age. Values of P < .05 were considered statistically significant.

RESULTS

The resident population of San Francisco in 1990

was 723 000. The age breakdown of the population, using 1990 US census data, was: younger than 1 year,

1 %; I to 4 years, 4%; 5 to 14 years, 8.5%; 15 to 24

years, 13%; and older than 24 years, 73.5%. There

were 273 total pediatric out-of-hospital CPAs during

the 48-month period from June 1989 to July 1993.

Sixty-five medical CPA patients met inclusion

cri-teria and underwent attempted paramedic

out-of-hospital resuscitation. Forty patients (62%) received

HDE, with a single dose range of 0.1 to 0.34 mg/kg

and a mean dose (±SD) of 0.19 ± 0.06 mg/kg; 19 of

these (47.5%) received at least one SDE dose before

HDE, and 21 (52.5%) received only HDE. Eight

chit-dren (20%) received HDE by the ET route only.

(4)

20%l

a

STANDARD DOSE HE

. NOTHERAPY

Fig 2. Distribution of the study population among HDE, SDE,

and NE groups.

904 I-UGH-DOSE EPINEPHRINE

teen patients (20%) received SDE with a single dose

range of 0.01 to 0.09 mg/kg, and a mean dose of 0.02

± 0.02 mg/kg. Two children (15%) received SDE by

the ET route only. Twelve patients (18%) received

NE. The distribution of the study population among

HDE, SDE, and NE groups is illustrated in Fig 2. The

HDE and SDE groups were statistically different

only in mean epinephrine dose (P < .0001), but not in

mean or median age, gender, proportion of asystolic

presenting rhythms, success of ET intubation or 10

line insertion, rate of ROSC, rate of ROER, survival,

or proportion of final diagnoses of sudden infant

death syndrome (SIDS) (Table 2).

Prehospital HDE Group

The median age of the HDE group was 0.25 years;

the mean age was 1 .87 years. There were 27 boys and

13 girls. Initial cardiac rhythms included one child

(3%) with PEA and an electrical heart rate of 30 beats per minute, 4 (10%) with VF, and the rest with asys-tole (87%).

Of 39 patients receiving HDE with asystole or VF,

4 (10%) experienced ROER. Three asystolic patients

developed PEA with rates of 60, 80, and 80 beats per

minute. One patient with VF (2.5%) developed a

perfusing bradycardia at 60 beats per minute; this

child was the only patient receiving HDE to

experi-ence ROER and ROSC in the field. The one child who

presented with PEA became asystolic after HDE.

Thirty-four of the 40 patients receiving HDE (85%)

were successfully intubated by paramedics in the

field, and 31 patients (77.5%) had functional JO lines

inserted. Nineteen patients (47.5%) received

elec-trical defibrillation, and 36 patients (90%) received atropine.

Prehospital SDE Group

The median age of the SDE group was 0.25 years,

and the mean age was 0.84 years. There were eight

boys and five girls. Three (23%) had PEA as their

initial rhythm, at rates of 10, 15, and 60 beats per

minute; two had VF (15%); and the remaining eight

patients (60%) had asytole.

Of 10 patients receiving SDE with asystole or VF, 2

(20%) experienced ROER. One patient with PEA

stayed in PEA at 12 to 15 beats per minute. One

patient with PEA and an initial heart rate of 60 beats

per minute went into a perfusing sinus rhythm at 113

beats per minute. An additional 2 patients with VF

(15.4%) stayed in VF and never developed ROER.

Only the child who converted to sinus rhythm

de-veloped ROER and ROSC in the field. One child with

pretreatment PEA at 10 beats per minute developed

asystole after SDE.

Twelve patients receiving SDE (92.3%) were

suc-cessfully intubated, and 9 patients (69.2%) had 10

lines successfully placed. Six (46.1 %) patients

re-ceived electrical defibrillation, and 10 patients

(76.9%) received atropine.

Prehospital NE Group

The median age of the NE group was 0.42 years,

and the mean age was I .04 years. There were 7 boys

and 5 girls. Of the 12 patients in this group, I (8%)

presented in PEA with a heart rate of 20 beats per

minute; this patient developed a perfusing sinus

rhythm with a heart rate of 150 beats per minute and

was the only child who received NE with ROSC in

the field. The remainder had asytole (92%), and none

developed ROSC or ROER.

One patient receiving NE (8%) had successful

placement of an 10 line, and two patients (17%) were successfully intubated. None of this group received

electrical defibrillation or drug therapy as part of

their resuscitation.

Overall Out-of-Hospital Experience

Figure 3 indicates the overall distribution of out-of-hospital presenting rhythms in the study

popula-tion. When stratified by age, the 54 children with

asystole (83% of the study group) had a median age

of 0.23 years; the 5 with PEA (8%), 0.25 years; and the

6 with VF (9%), 1.54 years. This age difference

be-tween VF and non-VF rhythm groups is statistically significant (P < .05). Figure 4 shows the overall

suc-cess rates for ET intubation (80%) in the 65 patients

with medical CPA, by age. Figure 5 shows the

suc-cess rates for 10 insertion (85%) in the medical

pa-tients, by age.

ED and Hospital Course and Outcome

Patients Receiving HDE

Three patients receiving HDE came to the ED with

organized electrical rhythms; two had presented in

asystole in the field and developed PEA after HDE

treatment; in the ED the PEA heart rates were 80

beats per minute in both children. One child

origi-nally in VF presented to the ED in sinus rhythm at

136 beats per minute. Only the patient with the sinus

rhythm sustained a detectable blood pressure in the

ED and survived to hospital discharge. This was a

16-month-old girl who presented in the field with VF

secondary to cocaine ingestion. She was eventually discharged from the hospital with spastic

quadriple-gia and profound mental retardation and a PCPC

score of 4 (severe disability with daily living mile-stones that are below the 10th percentile and exces-sive dependence on others for provision of activities of daily living). At follow-up 1 year later, the child still had a PCPC score of 4.

Twenty-two of the patients in the HDE group

(55%) were diagnosed by the coroner with SIDS.

(5)

AS’tSTOI.E

E iu.sst.ms ELECTRICAL ACTIVITY

U VENTRICULAR FIBRILLATION

Ui

z

14

12

10

8

6

4

2

0

II

TABLE 2. Comparison of Groups Receiving High-Dose Epinephrine and Standard-Dose

Epinephrine

Characteristic High-dose Epinephrine (N=40)

Standard-Dose Epinephrine (N=13)

P

Mean epinephrine dose 0.19 0.02 <0.0001

Median age 0.25 years 0.25 years 1.0 NS

Mean age

Gender (male/female)

1.87 years

27/13

0.84 years

8/5

0.48

0.74

NS

Asystole 35 8 0.055 NS

Endotracheal success 34 12 0.67 NS

Intraosseous success 31 9 0.71 NS

Return of spontaneous circulation I I 0.43 NS

Return of electrical rhythm 4/39 2/10 0.59 NS

Survival I I 0.43 NS

Sudden infant death syndrome 22 9 0.52 NS

NS, not significant.

Fig 3. Overall distribution of out-of-hospital presenting rhythms in the study population.

Four patients (10%) had asphyxia, four (10%)

pneu-monia, four (10%) congenital anomalies, 2 (5%)

upper airway obstruction, and three (7.5%)

miscel-laneous causes of death.

Table 3 presents the identifying features, success of and response to field and ED care, hospital course,

survival, and final diagnoses of the HDE group.

Patients Receiving SDE

Of the two patients receiving SDE who had an

organized electrical rhythm on ED presentation, only the patient with sinus rhythm had a detectable blood

pressure in the ED. She was a 3-month-old girl who

had presented with PEA in the field. She was

dis-charged neurologically intact with a diagnosis of

near-miss SIDS and represents the only healthy

sur-vivor in the entire study. At discharge and at

fot-low-up at age I year, she had a PCPC score of I

(age-appropriate

level of functioning,

devetopmen-tally appropriate).

Nine of the patients receiving SDE (69%) were

diagnosed with SIDS and three (23%) with

as-phyxia. Table 4 presents the identifying features,

success of and response to field and ED care,

hos-pital course, survival, and final diagnoses of the

SDE group.

Patients Receiving NE

The one patient receiving NE who developed a

perfusing sinus rhythm in the field after presenting

in PEA continued to have a perfusing sinus rhythm

k

0 0 0 0 0 (1) Cl) (I) U) Cl)

E E E E E

0 C’) (0 0) oJ C’, CD 0) c’J Cl)

PATiENT AGE

a

E1F

0 ElI SUCCESS

Fig 4. Overall success rates for El intubation (80%) in the 65 patients with medical CPA, by age.

in the ED. He was a I .25-year-old boy who ultimately

died in the hospital. The coroner’s diagnosis was

respiratory failure and Menke syndrome. He

re-ceived no ED treatment. Nine of the patients

receiv-ing NE (75%) were diagnosed with SIDS, one (8.3%)

with pneumonia, one (8.3%) with upper airway

ob-struction, and one (8.3%) with congenital

anaoma-lies. Table 5 presents the identifying features, success of and response to field and ED care, hospital course, survival, and final diagnoses of the NE group.

DISCUSSION Adult HDE Studies

During CPA, epinephrine will increase coronary

perfusion pressure and cerebral perfusion

pres-sure.18’2’3 In animal studies comparing HDE with

SDE, larger epinephrine doses will enhance

perfu-sion of the heart and brain further, with a

dose-response curve that peaks between 100 and 200 pg/

(6)

UAtternpt

0

0 Success

Ui

z

14

12

10

8

6

4

2

0

0 0 0 0 0 0 0 Cl) Cl) Cl) U) U) U) Cl) U)

E E E E E E E

0 (‘Cl ‘t CO 0 C’J C’J (0 0 04 (0

PATIENT AGE

Fig 5. Success rates for 10 insertion (85%) in the medical patients,

by age.

kg. Unfortunately, however, most human clinical

trials using HDE in CPA have shown no

improve-ment in survival when compared with SDE. Several

out-of-hospital studies have compared the success of

the two formulations on ROSC and ultimate survival

of adults in CPA.2628 In the largest published HDE

series, Stiell et at26 found no improvement in survival

or neurologic outcome in adult patients with CPA

treated with HDE. A subgroup of patents who

re-ceived HDE after 10 minutes of downtime were

sta-tistically less likely to survive. In a previous San

Francisco adult CPA trial comparing HDE and SDE,

Callaham et at28 found that HDE significantly

im-proved ROSC and hospital admission but did not

increase the hospital discharge rate or improve neu-rologic outcome.

Pediatric CPA Studies

Numerous investigators have studied pediatric

CPA, with documented survival from 1983 to 1993 of

4% to 21%.1h1 Unfortunately, some studies include patients with both respiratory and cardiac arrest. The total reported identified cardiac arrest or CPA cases in these studies is only 327, with a total of 40

survi-vors-giving an aggregate 12% CPA survival rate.

1-3,6,7,9-11 The small numerator and denominator in

this survivor ratio represent a major weakness in our

scientific foundations for pediatric resuscitation

rec-ommendations; there are not enough reported

pa-tients. Most of these pediatric studies demonstrate

tow ROSC, poor survival, and high probability of

significant neurologic injury among survivors (I I %

to 100%). In particular, out-of-hospital pediatric CPA has had a particularly low salvage rate. 25,811

In addition to the inadequate number of

docu-mented CPA cases, there are also many data

prob-lems. First, inclusion criteria and definitions of CPA are highly variable, so that existing studies report a

mix of children with respiratory arrest alone and

cardiac arrest, medical arrest, and traumatic arrest.

Often the type of arrest is not reported at all. Second,

reporting of core patient data elements is poorly

standardized, and presenting patient features with a

determinant effect on treatment response are not

consistently or reliably described (eg, site of CPA

and presenting rhythm). Third, ALS interventions

such as ET intubation and epinephrine

administra-tion are often incompletely or not specifically

de-scribed, confusing comparative analyses of benefits

of ALS procedures and drugs; a common pitfall is the

failure to document key characteristics of

epineph-rine administration, including both the route of

de-livery and doses per kilogram. The route of

admin-istration influences drug pharmcokinetics and may

be important for accurate comparison of treatment

groups; eg, a child receiving HDE by the ET route

may achieve epinephrine levels closer to anticipated

serum concentrations after SDE administration by

the IV or 10 route. Also, objective evaluation of a

drug effect requires reporting doses per kilogram

derived from a validated length-based resuscitation

tape or from actual weighing of the child. Finally,

almost every pediatric CPA study reports survival

alone as the endpoint; survivors’ outcomes are not

differentiated by short- and long-term neurotogic

status using quantifiable methods appropriate for

children, such as PCPC scores.

Our 3% survival rate is the lowest of all reported pediatric CPA studies. Although our high resuscita-tion failure rate may reflect deficiencies in overall treatment of pediatric CPA patients by San Francisco

community bystanders, the 91 I response system,

paramedics, or ED personnel, it instead may simply

represent our strict definition of CPA. Our CPA

in-clusion criteria, combined with intense base hospital

physician oversight of paramedic field practice,

at-tempted to carefully exclude all children without

true pulselessness. Earlier studies seem to have

over-estimated pediatric CPA survival significantly, in

part because of broadly defined CPA populations

that included some children who probably had not

experienced true cardiac arrest.

TABLE LEGEND

This legend applies to Tables 3, 4, and 5. A, asystole; At, atropine; B, bradycardia; bi, sodium bicarbonate; BP, blood pressure; Br, bretylium; CaCl, calcium chloride; CaG, calcium gluconate; D, dextrose; DC Shock, electrical countershock; Epi, epinephrine; ET,

endotracheal tube; Ex, expired; F, failure; G, glucose; HR. heart rate; 10, intraosseous line; IV, intravenous line; L, lidocaine; N, naloxone;

NA, not attempted; na, not applicable; Nor, norepinephrine; PEA, pulsesless electrical activity; 5, success; Sd, survived; SR, sinus rhythm;

Unk, unknown; VF, ventricular fibrillation; and VT, ventricular tachycardia.

*Estimated Weight; Unknown dose.

(7)

(8)

C

a s

U)

It)

LU

1

I-gJ

E

0

U.c;3.E

Io n

. <S

ca

#{149}0

I!

U.

a.

,

v,

0

Ce >c

3 . l,:t-;’ aeseess

c :. ti;w

.- 0’

= g #{149}

I.. 0

Cw

U W3

c

-- .

00

=

. . . .

0

. . . .

! #{176}#{176} 0

....

a

;; o <

....

-U-.

DOE a.

0.w

‘4,

-no <<

;.

- o

I-0 0 0 0 0 0 0 0 0 h

:<< <

C3 . #{163}

,-(V

-m

e-#{163}.&gg

§

0 ‘o E ZZ Z

-C3 0

--U. <<<<<<<<#{248};

U.--§hghs

ZZZZZZZZZ

Li-v) o

U , zzgg

g

z zzzzzzzzzggggggg

-.!:

.

!

.

U

2222222

QEe

CL

I

-=

u. t

©tc I

> - C) E

;.c<

=

0 0 0 0 0 0 0 0

< <.c<<<<<.c

w-= #{163}

I- ;

c

! r.. U)U)C

,‘

-za

( u. U.

4

c,

0

-t: 00

(9)

Previous Pediatric HDE Study

Enthusiasm for larger epinephrine doses in

chil-dren developed after Goeting and Paradis’ 1991

re-port24 on HDE in 20 pediatric CPA cases, which he

compared with 20 matched historical SDE control

subjects. Fourteen of the HDE group (70%) had

ROSC, whereas none of the SDE group had ROSC.

Eight children receiving HDE (40%) survived to

dis-charge, and 6 (30%) had regained prearrest

neuro-logic function at follow-up. They contended that

HDE provided a higher ROSC rate and a better

long-term outcome than SDE and urged that “HDE may

warrant incorporation into standard resuscitation

protocols at an early enough point to prevent

irre-versible brain injury.”24 Goetting and Paradis’ report

is the only previous comparison of HDE and SDE in

children, but its findings cannot be extrapolated to

the out-of-hospital setting. First, his HDE population

was a selected, hospitalized group with brief

down-times and early ALS treatment. His patients all had

witnessed CPAs in a monitored setting (although the

actual environment is not described), had mean

times to CPR of 3.4 minutes, and had epinephrine

administration within only 5 minutes of time of CPA.

In contrast, almost every patient in our series

suf-fered an unwitnessed CPA, with a long downtime

before CPR, ALS, and epinephrine administration.

Actual downtimes or preintervention times for our

patients were rarely known or recorded but were

obviously much longer than Goetting and Paradis’

witnessed CPA cases. The only patient characteristics

to help establish the time intervals from CPA to CPR

and ALS in our population were the lack of rigor

mortis, a crude measure of duration of pulselessness, and presenting heart rate and rhythm. Stratification

of downtimes of out-of-hospital CPA victims would

be helpful to correlate with clinical characteristics (eg, initial heart rate and rhythm) and for compari-son of responses to basic life support and ALS inter-ventions, but they are extremely difficult to obtain

accurately in the field, especially when the CPA is

unwitnessed.

Second, Goetting and Paradis’ patients receiving

HDE had mixed causes with possibly better

prog-noses than ours or other reported pediatric CPA

groups; eg, their HDE group had both trauma and

medical cases and only two SIDS cases (5%)#{149}24 In

contrast, we excluded all traumatic patients with

CPA and had 62% SIDS cases. Other pediatric CPA

studies also have failed to distinguish medical from

traumatic CPA and instead report all victims

to-gether. Separation of medical and traumatic causes

recognizes the important pathophysiologic and

treat-ment differences in these two pathways to CPA.

Epinephrine is unlikely to influence survival in

pe-diatric traumatic CPA and is not considered a

pri-mary therapy.37

Figure 6 illustrates causes-of-death categories in

the 65 patients with medical CPA in our study; these are typical causes for out-of-hospital medical CPA.2

5,8-11 These differences in causes in the two studies

emphasize the important distinctions between

in-hospital and out-of-hospital CPA populations.

None-theless, a specific cause may be less important than the prolonged period of profound hypoxia-ischemia

to the heart and brain that almost every patient in

our study had before epinephrine administration.

This common distinction between in-hospital versus

out-of-hospital CPA, duration of hypoxia-ischemia,

probably accounts for the strong association of the

site of CPA with outcome.

Third, Goetting and Paradis’ historical control sub-jects, the SDE cohort, were seperated from the

exper-imental HDE group by more than I year.24 This

feature of the study design poses a problem for

ac-curate comparisons of the groups, because of

possi-ble difficulties in the enforcement of consistent

as-sessments and interventions. Fourth, their HDE

cohort was small, and the statistical power of the

study is low. Our HDE group was twice as large but,

like the study of Goetting and Paradis, was not

ran-domized. Our epinephrine dosing was determined

by different attending physicians based on

radio-room wall chart guidelines and not strictly by

writ-ten protocol. Although our patients receiving SDE

and HDE were statistically similar groups, this

prob-lem in our retrospective study design may have

in-creased the possibility that our more viable patients

were more likely to receive HDE than SDE. The 1989

initiation date of our study created many such

ob-stacles to randomization and prospective study

de-sign, because only a few well-designed

out-of-hospi-tal studies had ever been conducted by then, and

none involved children. EMS officials were unfamil-iar with clinical research and unwilling to consent to

written out-of-hospital CPA protocols that were

in-consistent with contemporary ALS

recommenda-lions from the AHA. In the last 5 years, however, the research climate in many EMS regions has drastically changed, and original investigations are now

encour-aged in this still largely underappreciated

out-of-hospital clinical laboratory.

An important ambiguity in our data is the

group-ing of chidren by epinephrine dose, independently of

route of administration. The relative pharmacokinet-ics of epinephrine given the by ET, IV, and 10 routes

in the human child in CPA are not known, but the

current AHA recommendations suggest a 10-fold

in-crease in the ET epinephrine dose to obtain serum

levels comparable with SDE by IV or 10 delivery.12

USIDS LI Aspiyxi.

UPneumonIa

UCongenital anomalies

0 MIscellaneous 2% DUpperalrwayobstructfon

Fig 6. Causes-of-death categories in the 65 patients with medical

CPA in our study. These are typical causes for out-of-hospital

medical CPA.

(10)

Hence, our eight patients who received HDE ET,

including the only HDE survivor, may be also

cate-gorized with the SDE group. Because two children in

the SDE group also received only ET epinephrine, we

elected to separate the ET groups by dose. However,

restratifying the HDE survivor to the SDE category

would constitute a trend, although not statistically

significant because of the small sample size of the

study, of higher survival from SDE.

Last, Goetting and Paradis24 did not specifically describe patients’ initial heart rhythms or heart rates or link these features to patient outcomes. This

short-coming in his description of presenting rhythms is

especially important in the bradycardia group,

which may have included an unstated number of

perfusing patients with low-flow rather than no-flow states. Finally, his patients’ short- and long-term

neu-rologic outcomes are not recorded using objective,

standardized neurologic assessments, and long-term

outcomes are not documented at all.

Pediatric CPA Core Data Elements

Several recent authors and a consensus report

from a group of international investigators (the

Ut-stein Consensus Conference) have urged better

stan-dardization in reporting of these core elements in

adult CPA studies, to allow more objective

compar-isons between CPA groups and to minimize

interob-server differences.41 Consistency and

standardiza-tion in reporting valid core data elements are

imperative for meaningful future pediatric CPA

studies as well. A pediatric rendition of the adult

Utstein template, developed internationally, should

include at least the elements noted in Table 6:

resi-dent population of EMS system; pediatric age

cate-gories younger than 15 years; total out-of-hospital

pediatric CPAs per year; number of attempted

resus-citations; number of attempted medical

resuscita-tions; identifying patient features (age, gender, and measured weight); site of arrest; witnessed or

unwit-nessed; bystander CPR; downtime to CPR and ALS;

presenting rhythm and rate; out-of-hospital ALS

treatment and response; ED ALS treatment and

re-sponse; hospital admission; survival to hospital

dis-charge; final hospital or coroner’s diagnosis; and

short- and long-term neurologic outcome, using the

PCPC score.

Patient Categorization by Presenting Heart Rhythm and Rate

Based on our study, and other pediatric CPA

re-ports, the presenting heart rhythm and rate may

have the highest prognostic significance of all

pre-dictive variables.2’’5’9 For example, children with

asystole are extremely unlikely to experience

sus-tamed ROSC or neurologic survival. Eighty-three

percent of our group had asystole as their presenting

rhythm, and no child with asystole survived,

al-though two had temporary ROER in the field or ED.

This difference in survival between patients who

presented with asystolic versus nonasystolic

rhythms was statistically significant (P < .05). Others

have documented abysmal survival from asystole

similarly.2’’9

These findings argue for increased rigor in assess-ment, documentation, and categorization of different

CPA states based on presenting rhythm and rate. In

the out-of-hospital setting, patients’ initial heart

rhythms and heart rates may reflect duration of

hy-poxic-ischemic insult and offer useful, objective

prognostic information. The presenting rhythm and

rate may be a more accurate indicator of downtime,

TABLE 6. Pediatric Utstein Template: Suggested Core Data Elements for Pediatric

Cardiopulmo-nary Arrest Studies

I. Total resident population of emergency medical services system

2. Pediatric age categories (<15 years)

3. Total out-of-hospital pediatric cardiopulmonary arrests

4. Total attempted resuscitations

5. Total attempted medical resuscitations

6. Identifying patient features (age, gender, measured weight)

7. Site of arrest

8. Witnessed or unwitnessed?

9. Bystander cardiopulmonary resuscitation?

10. Downtimes (time intervals to cardiopulmonary resuscitation and advanced life support [ALS])

11. Presenting rhythm/rate 12. Out-of-hospital ALS treatment

a. Endotracheal intubation b. Electrical countershock

C. Vascular access and type (intravenous or intraosseous)

d. Initial epinephrine dose/measured body weight (kg) e. Route of delivery of epinephrine

f. Other drugs by kg weight, including route of delivery

13. Out-of-hospital response to ALS

a. Return of electrical rhythm (ROER)

b. Return of spontaneous circulation (ROSC) 14. Emergency department ALS treatment and response

15. Hospital admission

16. Survival to hospital discharge

17. Final hospital or coroner’s diagnosis

18. Survivors’ short-term neurologic status:

Pediatric Cerebral Performance Category (PCPC) score at discharge 19. Survivors’ long-term neurologic status:

Pediatric Cerebral Performance Category (PCPC) score at one year

(11)

true duration of pulselessness, and myocardial

re-sponsiveness than other characteristics, such as the

child’s temperature, estimated time interval to CPR,

and time interval to ALS, that are often available in

hospital but rarely reliable out of hospital. PEA

Further refinement of the PEA rhythm category

may be especially useful. PEA probably reflects

het-erogenous pathophysiologic states, which hold

dif-ferent prognostic significance.42’43 Bradycardia and

widening of the QRS complex on the

electrocardio-gram seem to represent the terminal phases of

elec-trical degeneration from profound

hypoxia-isch-emia. Our data suggest that children with slow (less

than 20 to 30 beats per minute), wide QRS complex

(greater than 0.10 seconds) rates may be more

logi-cally classified with asystolic patients within the

poor prognostic category of bradyasystole. None of

the four children in this study with initial slow, wide

QRS complex rhythms survived.

In our series, the two survivors both had some

form of electrical rhythm; one had narrow QRS

com-plex PEA and the other VF-highlighting the

prog-nostic importance of nonbradyasystolic

presenta-tions. Narrow QRS complex PEA may have the best

prognosis of all CPA rhythms, particularly if the rate

is more than 30 to 40 beats per minute. Overall,

although we had five patients with the presenting

rhythm of PEA, only one patient, the eventual

sur-vivor, had an initial narrow QRS complex rate of

more than 40 beats per minute. Children with

nar-row QRS complex PEA may have low-flow rather

than no-flow perfusion states that may be more

likely to respond to ALS. Indeed, some of these

chil-dren may have blood pressures simply not

detect-able by paramedics using palpation techniques and

blood pressure cuffs in noisy, chaotic field circum-stances.

SW’ and VT

There were no children in our study with SVT or

VT as the presenting rhythm, confirming the rarity of

these rhythm presentations in out-of-hospital CPAs.

VF

VF, a purportedly rare pediatric CPA rhythm,

occurrred in six (9%) of our patients. This group

was older (median age, I .54 versus 0.25 years for

non-VF patients; P < .05), had a trend toward

middle childhood ages, and had more non-SIDS

diagnoses (4 of 6) compared with the non-VF

group (21 of 59). The presence of congenital heart

disease, increasing cardiac mass, and maturation

of -adrenergic receptors in the heart with

advanc-ing age after infancy may be partly responsible for

this apparent higher susceptibility of older

chil-dren for VF.4446 All six patients with VF in this

study were defibrillated as part of the initial

resus-uscitation, yet our 17% overall survival rate and

zero intact neurologic survival is less than the 25%

to 30% VF intact survival in the general

litera-ture.4749 The reported out-of-hospital experience

with pediatric VF, however, is small.

Our data suggest that out-of-hospital VF may

rep-resent a more ominous rhythm state in children than

has been previously recognized. The AHA

recom-mends initial electrical therapy for pediatric VF, with epinephrine administration second.

Paramedic ALS Interventions

Out-of-hospital placement of ET tubes and 10 lines

should be part of standard field pediatric ALS care

and may allow more rational treatment, triage, and

transport policies and protocols for pediatric CPA.

As noted in Figs 4 and 5 and in other out-of-hospital

studies, paramedics are quite successful with these

pediatric field procedures.#{176}55 Hence, for pediatric

patients who have failed out-of-hospital medical

CPA treatment, the ED has few additional

interven-tions to offer. In some EMS regions, on-line medical direction by radio or telephone also allows further

physician oversight of paramedics for treatment,

tri-age, and transport decisions.

Proposal for Out-of-Hospital Treatment, Transport, and Termination of Resuscitation

Our data suggest several modifications of out-of-hospital pediatric CPA treatment. First, patients with medical CPA should be stratified, based on objective,

simple electrocardiographic data-initial heart

rythm and rate and QRS width. Children with

bra-dyasytolic presenting rhythms (asystole or slow,

wide QRS complex PEA < 20 to 30 beats per minute)

have an extremely poor prognosis. If no extenuating circumstance such as hypothermia or sedative-hyp-notic drug overdose exists, a limited resuscitation

should be considered. A reasonable level of field

resuscitation for bradyasystolic patients might

in-dude paramedic ET intubation with vigorous

oxy-genation and ventilation, 10 line placement, delivery of two or three doses of epinephrine, and

reassess-ment; the appropriate epinephrine dose for this

group is unknown.

At reassessment, if the child has not converted to a viable, nonbradyasytolic rhythm, out-of-hospital ter-mination of the resuscitation and notification of the

coroner from the scene without hospital transport

should be considered. If the recommended ALS

in-terventions cannot be performed in the field, then

hospital transport is usually indicated. If resuscita-tion is stopped, and the child is left with the coroner,

it is imperative that immediate grief services be

of-fered to the family and critical incident stress

debrief-ing provided to the paramedic and ambulance

alien-dants.

On the other hand, if after treatment the child

develops a nonbradyasystolic rhythm (ie, sinus

rhythm, PEA, SVT, or VT), or if the child develops

VF, then specific ALS is indicated along with

ambu-lance transport to a hospital ED.

If the child presents with a nonbradyasystolic

rhythm, the treatment should be based on the

spe-cific features of the rhythm and heart rate. For

exam-ple, treatment of narrow QRS complex PEA should

emphasize SDE administration, aggressive fluid

re-suscitation, and correction of obstructive conditions (eg, tension pneumothorax and cardiac tamponade).

(12)

Treatment of pulseless SVT, pulseless VT, and VF

should prioritize electrical countershock, then careful

SDE and lidocaine administration for VT and VF.

Sometimes ambulance transport is indicated for

bradyasystolic children who fail ALS. These

chil-dren, who need hospital transport for family grief

counseling and medicolegal or other family

psycho-social purposes, should be transported in a normal,

less-dangerous response mode without further

ex-pensive and unnecessary field or ED treatment.

Using this treatment algorithm in our study

pa-tients would have resulted in hospital ED transport

of seven patients (10%) and field termination of

re-suscitaion in 90%. This would have significantly

re-duced unnecessary risks and major resource

commit-ment to an apparently unsalvageable patient group.

Light-and-siren transport through urban areas is

fraught with expense and safety hazards to the

am-bulance occupants and to the citizenry. Transport of

refractory bradyasystolic children who have failed

field ALS may have greater mathematical probability of death or serious disability to innocent bystanders

or prehospital personnel than meaningful patient

survival. Such a transport algorithm has been

advo-cated by numerous authors of adult CPA reports, in

light of similar resuscitation failure rates among

adult CPA victims who fail field ALS.M

Moreover, the cost of such hopeless interventions

is enormous. Charges for attempted resuscitation of

a child in CPA receiving conventional ALS interven-tions in the field, ambulance transport, and standard

ED treatment before pronouncement of death are

approximately $2800 in San Francisco in 1995. Futile

adult resuscitation attempts in one study resulted in

more than 2 hours of nurses’ time and more than 45

minutes of physicians’ time. Staff time associated

with pediatric resuscitations has not been studied

but may be even longer than for adult resuscitations.

If a child experiences temporary ROSC in the ED and

is admitted to a hospital intensive care unit, the costs

are greatly increased. For a child such as our HDE

survivor, who was discharged with profound

neuro-logic disabilities, the costs of medical and supportive care over a lifetime are millions of dollars.

CONCLUSIONS

HDE, in doses of 100 to 200 pg/kg, does not seem

to improve survival from out-of-hospital CPA,

com-pared with SDE, in doses less than 100 pg/kg.

Out-of-hospital pediatric CPA has a grim

progno-sis, probably related to long periods of

hypoxia-ischemia that seem to be almost universal in this

population before initiation of CPR and ALS.

Pre-senting heart rate and rhythm and width of QRS

complex may reflect duration of hypoxic-ischemic insult and offer an objective basis for treatment and

prognosis, especially in unwitnessed CPA cases in

which downtime or preintervention times are rarely known.

Ninety percent of pediatric patients with CPA will

have bradyasystolic presentations and may be

can-didates for either no resuscitation attempts in the

field or limited attempts with field termination.

Ap-propriate pediatric education of paramedics, grief

counseling services for families, and critical incident

stress debriefing must be part of local EMS plans for

field termination of pediatric resuscitation.

A large multicenter, blinded clinical trial with

ad-equate statistical power is needed to compare SDE

and HDE, optimally in a nonbradyasystolic CPA

population, to define optimal doses, safety, and

pa-tient survival characteristics and to reassess the pre-liminary conclusions of this retrospective analysis.

An essential feature for all future investigations of out-of-hospital pediatric CPA is standardized report-ing of core data elements, similar to the Utstein Style

template,35 currently being advocated for adult CPA

studies. The pediatric Utstein template should

in-dude the following: resident population of the EMS

system; pediatric age categories younger than 15

years; total out-of-hospital pediatric CPAs per year;

number of attempted resuscitations; number of

at-tempted medical resuscitations; identifying patient

features (age, gender, and measured weight); site of

arrest; witnessed or unwitnessed; bystander CPR;

downtime to CPR and ALS; presenting rhythm and

rate; out-of-hospital ALS treatment and response; ED

ALS treatment and response; hospital admission;

survival to hospital discharge; final hospital or

cor-oner’s diagnosis; and short- and long-term

neuro-logic outcome, using the PCPC score.

ACKNOWLEDGMENTS

We thank Joan Hu for her splendid work preparing the manu-script and Paul Ishimine for his capable assistance gathering the

data.

REFERENCES

1. Lewis JK, Minter MG, Eshelman SJ, Witte MK. Outcome of pediatric resuscitation. Ann El7:t’rg Med. 1983;12:297-299

2. Eisenberg M, Bergner L, Hallstrom A. Epidemiology of cardiac arrest

and resuscitation in children. Ann Etucrg Med. 1983;12:o72-o74

3. Torphy DE, Minter MG, Thompson BM. Cardiorespiratory arrest and resuscitation of children. Am IDis Child. 1984;138:1099-1 102 4. Ludwig 5, Kettrick RG, Parker M. Pediatric cardiopulmonary

resusci-tation. C!i,z Pediatr. 1984;23:71-75

5. Nichols DC, Kettrick RG, Swedlow DB, et al. Factors influencing

out-come of cardiopulmonary resuscitation in children. Pediatr El?1t’rg Cart’.

1986;2:l-5

6. Gillis 1’ Dickson D, Rieder M, et al. Results of inpatient pediatric

resuscitation. Crit Cart’ Med. 1986;14:469-471

7. O’Rourke PP. Outcome of children who are apneic and pulseless in the

emergency room. Crlf Care Med. 1986;14:466-468

8. Fiser DH, Wrape V. Outcome of cardiopulmonary resuscitation in chil-dren. Pediatr E;nerg Care. 1987;3:235-238

9. Zaritsky A, Nadkarni V. Getson P, Kuehl K. CPR in children. Ann Emerg

Med. 1987;16:1 107-1111

10. Thompson JE, Bonner B, Lower GM. Pediatric cardiopulmonary arrests

in rural populations. Pediatrics. 1990;86:302.-306

11. Schoenfeld PS, Baker MD. Management of cardiopulmonary and trauma resuscitation in the pediatric emergency department. Pediatrics.

1993;91 :726-729

32. American Heart Association. Standards for cardiopulmonary

resuscita-tion and emergency cardiac care. JAMA. 1992;268:2251-2275

13. Silverman BK, ed. APLS. The Pediatric Emergency Medicine Course. 2nd ed. Elk Grove Village, IL: American Acadamy of Pediatrics & American College of Emergency Physicians; 1993

14. Chameides L, ed. Textbook of Pediatric Advanced Life Support, Dallas:

American Heart Association; 1988

15. ZLaritsky A. Pediatric resuscitation pharmacology. Atit: E;nerg Med. 1993;

22:445-455

16. Brown CG, Werman HA. Adrenergic agonist during cardiopulmonary resuscitation. Resuscitation.1990;19:1-16

17. Seidel J.Pediatric cardiopulmonary resuscitation: an update based on

(13)

the new American Heart Association guidelines. Pediatr Emerg Care.

19939:98-103

18. Kosnik JW, Jackson RE, Keats 5, et al. Dose-related response of centrally administered epinephrine on the change in aortic diastolic pressure during closed-chest massage in dogs. Ann Emerg Med. 1985;14:204-208 19. Otto CW, Yakaitis RW. The role of epinephrine in CPR. A reappraisal.

Ann Emerg Med. 1984;13:840-843

20. Paradis NA, Martin GB, Rosenberg J, Rivers EP, Goetting MG. The effect of standard and high dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation. JAMA. 1991; 265:1139-1144

resuscita-hon and emergency cardiac care. JAMA. 1980;244:472-500

resuscita-lion and emergency cardiac care. JAMA. 1986;255:2954-2969

23. Goetting MG, Paradis NA. High-dose epinephrine in refractory pediat-nc cardiac arrest. Crit Care Med. 1989;17:1258-1262

24. Goetting MG, Paradis NA. High-dose epinephrine improves outcome from pediatric cardiac arrest. Ann Emerg Med. 1991;20:22-26

25. Durbin DR. Update on pediatric cardiopulmonary resuscitation. Hosp Physician. 199430:14-22

26. Shell IC, Hebert PC, Weitman BN. High-dose epinephrine in adult cardiac arrest. N Engi JMed. 1992327:1045-1050

27. Brown CC, Martin DR, Pepe FE. A comparison of standard-dose and

high-dose epinephrine in cardiac arrest outside the hospital. N Engi I

Med. 1992327:1051-1055

28. Callaham M, Madsen CD, Barton CW, et al. A randomized clinical trial

of high-dose epinephrine and norepinephrine vs standard-dose

epi-nephrine in prehospital cardiac arrest. JAMA. 1992;268:2667-2672 29. Lindner KB, Ahnfeld FW, Prengel AW. Comparison of standard and

high dose adrenaline in the resuscitation of asystole and electromechan-ical dissociation. Acta Anaesthesiol Scand. 1991;35:253-256

30. Gausehe M, Henderson DP, SeidelJS. Vital signs as part of the prehos-pital assessment of the pediatric patient. A survey of paramedics. Ann Emerg Med. 1990;19:173-178

31. Fiser DH. Assessing outcome of pediatric intensive care. I Pediatr.

1992;121:68-74

32. Michael JR. Guerci AD, Koehler RC, et at. Mechanisms by which epi-nephrine augments cerebral and myocardial perfusion during

cardio-pulmonary resuscitation in dogs. Circulation. 1984;69:822-835

33. Koehler RC, Michael JR. Guerci AD, et al. Beneficial effect of

epineph-rine infusion on cerebral and myocardial blood flows during CPR. Ann

Emerg Med. 1985;14:744-749

34. Brown CC, Werman NA, Davis EA, et al. The effect of graded doses of epinephrine on regional myocardial blood flow during cardiopulmo-nary resuscitation in swine. Circulation. 1981;79:491-497

35. Brown CC, Taylor RB, Werman HA, et al. Effect of standard dose of epinephrine on myocardial oxygen delivery and utilization during

car-diopulmonary resuscitation. Crlf Care Med. 1988;16:536-539

36. Brown CC, Werman HA, Davis EA, et al. Comparative effects of graded

doses of epinephrine on regional brain blood flow during CPR in a

swine model. Ann Emerg Med. 1986;15:1138-1144

37. Ramenofsky ML and Dieckmann RA. Prehospital trauma management.

In: Dieckmann RA, ed. Pediatric Emergency Care Systems: Planning and

Management. Baltimore, MD: Williams & Wilkins; 1992:203-211 38. Cummins RO, Chamberlain DA. The Utstein Abbey and survival from

cardiac arrest: what is the connection? (editorial). Ann Emerg Med.

1991;20:918-919

39. Eisenberg MS, Horwood BD, Cummins RO, et at. Cardiac arrest and resuscitation: A tale of 29 cities. Ann Emerg Med. 1990;19:179-186

40. Cummins RO, Chamberlain DA, Abramson NS, et al. Recommended

guidelines for uniform reporting of data from out-of-hospital cardiac

arrest: the Utstein style. Ann Emerg Med. 1991;20:861-874

41. Eisenberg MS. Cummins RO, Larsen FL. Numerators, denominators,

and survival rates: reporting survival from out-of-hospital cardiac arrest. Am IEmerg Med. 19919544-546

42. Stueven HA, Aufderheide T, Waite EM, et al. Electromechanical

dissociation: six years prehospital experience. Resuscitation. 1989;17:

173-182

43. Vanags B, Thakur RK, Stueven HA, et al. Interventions in the therapy of

electromechanical dissociation. Resuscitation. 1989;17:163-171

44. Walsh CK, Krongrad E. Terminal cardiac electrical activity in pediatric patients. Am ICardiol. 198351:557-561

45. Friedman W. The intrinsic physiologic properties of the developing heart. Prog Cardiovasc Dis. 1972;15:87-111

46. Rosen MR. Hordof AJ, Ilvento JP, Danio P Jr. Effect of adrenergic amines on electrophysiological properties and automaticity of neonatal and adult canine Purkinje fibers: evidence for aand b adrenergic action.

Circ Res. 1977;40:390-400

47. Weaver WD, Cobb LA, Hallstrom AP, et al. Considerations for

improv-ing survival from out-of-hespital cardiac arrest. Ann Emerg Med. 1986;

15:1181-1186

48. Aprahamian C, Thompson BM, Gruchow HW, et al. Decisionmaking in

prehospital cardiac arrest. Ann Emerg Med. 1986;15:445-449

49. Myerburg RJ, Kessler KM. Zaman L, Conde CA, Castellanos A. Survi-vors of prehosital cardiac arrest. JAMA. 1982;247:1485-1490

50. Pointer JE. Clinical characteristics of paramedics’ performance of

pedi-atric endotracheal intubation. Am JEmerg Med. 1987;7:364-366

51. Aijian F, Tsai A, Knopp R, et al. Endotracheal intubation of pediatric

patients by paramedics. Ann Emerg Med. 1989;18:489-494

52. Losek JD, Bonadio WA, Walsh-Kelly C, et al. Prehospital pediatric endotracheal intubation performance review. Pediatr Emerg Care. 1989; 5:1-4

53. Seigler RS, Techlenburg FW, Shealy R. Prehospital intraosseous infusion

by emergency medical services personnel. Pediatrics. 1987;84:173-177

54. Smith RJ, Keseg DP, Manley LK. Intraosseous infusions by pre-hospital

personnel in critically ill pediatric patients. Ann Emerg Med. 1988;17:

491-495

55. Miner WF, Corneli HM, Bolte RG, et at. Prehospital use of intraosseous

infusion by paramedics. Pediatr Emerg Care. 19895:5-7

56. Kellerman AL, Hackman BB, Somes C. Predicting the outcome of

un-successful prehospital advanced cardiac life support. JAMA. 1993;270:

1433-1436

57. Bonnin MJ, Pepe FE, Kimball KT, Clark PS. Distinct criteria for

termi-nation of resuscitation in the out-of-hospital setting. JAMA. 1993a70:

1457-1462

58. Gray WA, Capone RJ, Most AS. Unsuccessful emergency medical

re-suscitation-are continued efforts in the emergency department

justi-fled? N Engl IMed. 1991325:1393-1398

59. Bonnin MJ, Swor RA. Outcomes in unsuccessful field resuscitation

attempts. Ann Emerg Med. 1989;18:507-512

60. Kellerman AL, Staves DR. Hackman BB. In-hospital resuscitation fol-lowing unsuccessful prehospital advanced cardiac life support: “heroic

efforts” or an exercise in futility? Ann Emerg Med. 1988;17:589-594

61. Wolford RW, Kaplan RM, Stewart RD. Paris PM. ALS witnessed pro-hospital cardiopulmonary arrest (abstract). Ann Emerg Med. 1988;17:410

62. Jakobsson J, Nyquist 0, Rehnqvist N, et al. Prognosis and clinical follow-up of patients resuscitated from out-of-hespital cardiac arrest.

Acta Med Scand. 1987;222:123-132

63. Geehr PC, Lewis FR, Auerback PS. Failure of open-heart massage to improve survival after prehospital nontraumatic cardiac arrest. N EngI

IMed. 1986;314:1189-1190

64. Warner LL, Hoffman JR. Baraff U. Prognostic significance of field response in out-of-hospital ventricular fibrillation. Chest. 1985;

87:22-28