Drogas y PCR - Urgencia UC

Drogas en PCR
Pablo Aguilera F
Programa de Medicina de Urgencia
P. Universidad Católica de Chile
Curso de Reanimación para Residentes
Historia y antecedentes
• Alta mortalidad
• 75% causas cardiovasculares primarias
• A pesar de avances la mortalidad es alta
• Cifras decepcionantes
Continue CPR
30
2
Defibrillation
Importance of CPR
ACLS
DF in <8 min
Bystander CPR
Early access
0
1
2
3
4
5
6
7
Odds Ratio
Stiell (2005) N Engl J Med
Presión
perfusión
Coronary Perfusion Pressure (CPP)
Key to coronaria
Successful Resuscitation
Presión de perfusión
coronaria= PPC
Aod
CPP = Aod - RAd
PPC=PAod- PAud
RAd
¿Para que sirven las
drogas?
• Tener en cuenta que PCR = Flujo CERO
•
NO SIRVEN DE MUCHO EN RELACION
A EVIDENCIA DURA
Three-Phase Model of Resuscitation
Weisfeldt ML, Becker LB. JAMA 2002: 288:3035-8
100%
Myocardial ATP
0
Circulatory
Phase
Electrical
Phase
0
2
4
6
8
Metabolic
Phase
10
12
Arrest Time (min)
14
16
18
20
OPALS
•
•
•
•
•
Ontario Prehospital Advanced Life Support
trial
Programa de desfibrilación rápida + ACLS
5638 pacientes
Conclusión: La suma de ACLS (drogas cardioactivas) a programa de desfibrilación,
aumenta ROSC y admisión al hospital.
No mejora sobrevida al alta.
Algoritmo ACLS AHA 2010
Neumar R W et al. Circulation 2010;122:S729-S767
Copyright © American Heart Association
Algoritmo circular ACLS AHA 2010
Neumar R W et al. Circulation 2010;122:S729-S767
Copyright © American Heart Association
Drogas utilizadas en RCP
• Vasopresores
• Antiarrítmicos
• Buffers
• Otras: Estrógenos, nitroprusiato
Alternativas de
Administración
• Oro- traqueal
• Endovenosa
• Intraósea
Importancia de “llenar
la bomba”
Importance of “Priming the Pump”
Importance
of
Priming
the
Pump
Importance
“Priming
the
Pump
Importance
of
the
Pump
Importance
of
““Priming
the
Pump
” ””””
Importance
of
“Priming
Priming
the
Pump
Importance of “Priming the Pump”
Myocardial Cell
Myocardial
Cell
Myocardial
Myocardial
Cell
Myocardial
Cell
Myocardial
Cell
Myocardial
CellCell
100%
ATP 100% ATP
100%
ATP
100%
ATP
100%
ATP
100%
100%
ATPATP
Myocardial
Myocardial
Cell
Myocardial
Cell
Myocardial
Cell
Myocardial
Cell
Myocardial
Cell
Myocardial
CellATPCell
<10%
<10%
ATP
<10%
ATP
<10%
ATP
ATP
<10%
ATP
<10% ATP
Myocardial
Cell
Myocardial
Myocardial
CellCell
Myocardial
Cell
Myocardial
Cell
Myocardial
Cell
Myocardial
30-40%
ATP
30-40%
ATP
30-40%
ATP
30-40%
ATP
30-40%
ATP
30-40% ATP
Cell
30-40% ATP
Perfusión miocárdica:
• Δ de perfusión de P°D
• Estenosis coronaria
Area under the curve (yellow) measurement of
“integrated CPP” was 59,223 mm
Hg*dt seconds in A (continuous chest
compressions) and 35,737 mm Hg*dt seconds
in B (interrupted chest compressions). This
calculates to a 40% decrease in the
integrated area CPP (iCPP) with the interrupted
chest compressions.
Masaje Torácico
Figure 9-2 • Aortic and right atrial pressure tracings demonstrating the coronary
perfusion pressure gradient during the relaxation phase of chest compressions. Note
the rapid fall off in the diastolic gradient with the cessation of chest compressions,
and the time required to “rebuild” a maximal CPP after such interruption.
Compresiones torácicas
• Interrupciones afectan PPC generada en el
ciclo
• Las 1° 5-10 CC inician el ΔPPC , óptimo al
final de la serie
• Al cesar baja a 0 en 5’’
• Al reiniciar se repite el ciclo
Drogas utilizadas en RCP
• Vasopresores
• Antiarrítmicos
• Buffers
• Otras: Estrógenos, nitroprusiato, corticoides,
betabloqueo.
18
Vasopresores
• Adrenalina
• Vasopresina
• Atropina
Vasopresores
• Evidencia que aumenta la recuperación de
pulso. ( ROSC)
• No hay trabajos RCT´s que mejore
sobrevida o outcome neurológico en este
tópico en cualquier ritmo.
Adrenalina
• Agente simpático-mimético
• Efecto α y β
• α 1 y α 2:
Perfusión
•
•
β 1:
•
•
Vasocontricción arterial ---
coronaria
Aumenta contractilidad miocárdica.
Aumenta el consumo de 02
Emergency Medicine International
CPR (indepth, alon, minavoiding
se of ther-
g delivery,
use signifdefibrilla-
ental and
gs during
gs such as
e, fibrino-
ssue hypn supply-
Figure 1: Schematic representation of the action of epinephrine
on intracellular calcium in myocytes. ATP: adenosine triphosphate,
cAMP: cyclic adenosine monophosphate, Gs: G protein complex, IP: inositol phosphate, PIP2 : phosphoinositol diphosphate,
Vasopresores
•
β 2:
•
•
estimula relajación de musculatura lisa
disminuye la presión de perfusión
coronaria
For reprint orders, please contact: [email protected]
University of Arizona College of Medicine, Tucson, AZ, USA
Author for correspondence: University of Arizona Sarver Heart Center, University of Arizona, Tucson, AZ, USA
Tel.: +1 520 626 2000 Fax: +1 520 626 0964 [email protected]
1
†
The use of epinephrine during cardiac arrest has been advocated for decades
and forms an integral part of the published guidelines. Its efficacy is supported
by animal data, but human trial evidence is lacking. This is partly attributable to
disparities in trial methodology. Epinephrine’s pharmacologic and physiologic
effects include an increase in coronary perfusion pressure that is key to successful
resuscitation. One possible explanation for the lack of epinephrine’s demonstrated
efficacy in human trials of out-of-hospital cardiac arrest is the delay in its
administration. A potential solution may be intraosseus epinephrine, which can
be administered quicker. More importantly, it is the quality of the basic life
support, early and uninterrupted chest compressions, early defibrillation and
postresuscitation care that will provide the best chance of neurologically
intact survival.
• Utilizada en pacientes refractarios al
SHOCK eléctrico.
• Su uso data desde aprox. 100 años
• Ventajas y desventajas asociadas a su uso
Epinephrine administration has been advocated during resuscitation of cardiac arrest
for decades [1–5] . The 2005 guidelines by
both the American Heart Association and
the European Resuscitation Council recommend its use [6–8] . Surprisingly, definitive evidence for epinephrine’s efficacy in humans
is lacking. As with many components of the
Guidelines for Cardiopulmonary Resuscitation
and Emergency Cardiac Care, its recommendation is largely based on tradition and its
success in animal models. Conflicting results
between animal and human research are due
to the disparate methodology and populations
studied, as well as the duration of untreated
and treated cardiac arrest prior to epinephrine
administration. The purpose of this article is
As early as 1906, Crile and Dolley noted the
importance of an adequate aortic diastolic pressure during attempted cardiac resuscitation [11] .
They stated that it often was not possible to
achieve an adequate aortic diastolic pressure
without the addition of epinephrine.
Since epinephrine has both inotropic and
chronotropic effects on the beating heart and
also produces peripheral vasoconstriction, there
was confusion regarding which of these effects
was the most important. Epinephrine increases
the peripheral vascular resistance, transiently
decreasing perfusion to most of the body, but in
the process increases the aortic diastolic pressure
and perfusion to the heart.
The classic studies of Pearson and Redding
performed in the 1960s merit emphasis [12–14] .
Review
Robert R Attaran1 & Gordon A Ewy†
Future Cardiology
Epinephrine in resuscitation: curse
or cure?
Altas dosis de Adrenalina
R E P E AT E D H I G H D O S E S A N D STA N DA R D D O S E S O F E P I N E P H R I N E F O R C A R D I AC A R R E ST O U T S I D E T H E H O S P I TA L
A COMPARISON OF REPEATED HIGH DOSES AND REPEATED STANDARD DOSES
OF EPINEPHRINE FOR CARDIAC ARREST OUTSIDE THE HOSPITAL
PIERRE-YVES GUEUGNIAUD, M.D., PH.D., PIERRE MOLS, M.D., PH.D., PATRICK GOLDSTEIN, M.D., EMMANUEL PHAM, M.D.,
PIERRE-YVES DUBIEN, M.D., CARINE DEWEERDT, PH.D., MICHEL VERGNION, M.D., PAUL PETIT, M.D.,
AND PIERRE CARLI, M.D., FOR THE EUROPEAN EPINEPHRINE STUDY GROUP*
ABSTRACT
Background
Clinical trials have not shown a benefit of high doses of epinephrine in the management
of cardiac arrest. We conducted a prospective, multicenter, randomized study comparing repeated high
doses of epinephrine with repeated standard doses
in cases of out-of-hospital cardiac arrest.
Methods Adult patients who had cardiac arrest outside the hospital were enrolled if the cardiac rhythm
continued to be ventricular fibrillation despite the
administration of external electrical shocks, or if they
had asystole or pulseless electrical activity at the
time epinephrine was administered. We randomly
assigned 3327 patients to receive up to 15 high doses
(5 mg each) or standard doses (1 mg each) of epinephrine according to the current protocol for advanced cardiac life support.
Results In the high-dose group, 40.4 percent of
1677 patients had a return of spontaneous circulation,
as compared with 36.4 percent of 1650 patients in the
standard-dose group (P=0.02); 26.5 percent of the
patients in the high-dose group and 23.6 percent of
those in the standard-dose group survived to be admitted to the hospital (P=0.05); 2.3 percent of the patients in the high-dose group and 2.8 percent in the
standard-dose group survived to be discharged from
the hospital (P=0.34). There was no significant difference in neurologic status according to treatment
among those discharged. High-dose epinephrine improved the rate of successful resuscitation in patients
with asystole, but not in those with ventricular fibrillation.
Conclusions In our study, long-term survival after
cardiac arrest outside the hospital was no better with
repeated high doses of epinephrine than with repeated standard doses. (N Engl J Med 1998;339:1595-601.)
To pursue this question further, we conducted a
prospective, multicenter, randomized, double-blind
study to compare the efficacy of repeated 1-mg doses
of epinephrine with that of repeated 5-mg doses of epinephrine in adults with out-of-hospital cardiac arrest.
METHODS
The French and Belgian Emergency Medical Systems
Cardiac arrest occurring outside the hospital in France and Belgium is managed by the Service d’Aide Médicale Urgente.14,15
Each medical region has a dispatching center located in a major
hospital that controls several units, called Services Mobiles d’Urgence et de Réanimation, that are based in other hospitals within
the region. Each hospital is equipped with several ambulances
that carry a physician, a nurse, and a trained driver. The telephone
number is a national emergency number. Switchboard operators,
available 24 hours a day, receive all calls related to cardiac arrest
in the dispatching centers and forward them to the dispatching
physician, who decides whether to send out a team of emergency
medical technicians (who are members of the fire-department rescue services) and, at the same time, an ambulance staffed by the
medical team. Because of the greater numbers of emergency medical technicians, they are frequently closer to the patient and can
start basic life support before the arrival of the medical team. The
medical units provide advanced cardiac life support, according to
the American Heart Association guidelines adapted for Europe by
the European Resuscitation Council, until a return of spontaneous
circulation is observed on the scene or a decision is made by the
team physician to stop cardiopulmonary resuscitation.
Mayor ROSC y admisión hospitalaria.
Sin diferencias en mortalidad ni outcome
neurológico
Study Design
The study was approved by the ethics committees of the university hospitals in Lyons and Brussels and by the Consultative Council
for the Protection of Persons Volunteering for Biomedical Research
of our institution; approval was valid for each of the participating
study centers. Waiver of informed consent was accepted by the
council because of the urgency of the situation of the subjects with
cardiac arrest and the lack of availability of family members.
©1998, Massachusetts Medical Society.
E
PINEPHRINE remains the first-line adrenergic agent used for cardiac arrest, but the
dose remains controversial.1-3 Almost all experimental studies suggest that high-dose epinephrine is more effective than the currently recommended doses; higher doses increase myocardial and
cerebral blood flow and improve rates of survival in
animals.4-9 In contrast, with the exception of a recent
multinational study,10 multicenter clinical trials have
From the Department of Anesthesiology and Emergency Medical System,
Service d’Aide Médicale Urgente of Lyons, Edouard Herriot Hospital,
Claude Bernard University, Lyons, France (P.-Y.G., P.-Y.D., P.P.); the Department of Emergency Medicine and Emergency Medical System, Service
d’Aide Médicale Urgente of Brussels, Centre Hospitalier Universitaire
Saint-Pierre, Brussels, Belgium (P.M.); the Department of Anesthesiology
and Emergency Medical System, Service d’Aide Médicale Urgente of Lille,
Centre Hospitalier Régional et Universitaire of Lille, Lille, France (P.G.);
the Department of Computers and Statistics, Medical Service, Claude
Bernard University, Lyons, France (E.P.); the Pharmaceutical Department,
Edouard Herriot Hospital, Lyons, France (C.D.); the Department of
Emergency Medicine, Service Mobile d’Urgence et de Réanimation of the
Centre Hospitalier Régional Citadelle, Liege, Belgium (M.V.); and the De-
mittees, Crown Law and Guardianship Boards, the concerns of
our findings. However we considered this trial needed to be pragbeing involved in a trial in which the unproven “standard of care”
matic in having few exclusion criteria, recognising that the timing
was being withheld prevented four of the five ambulance services
of drug administration will vary depending on the successful estabfrom participating. In addition adverse press reports questionlishment of intravenous access and variations in the resuscitation
ing the ethics of conducting this trial, which subsequently led to
processes of care including CPR quality. This, in essence reflects
the involvement of politicians, further heightened these concerns.
current clinical practice. As blinding was well preserved in this
Despite the clearly demonstrated existence of clinical equipoise for
study we consider the likelihood of these factors being differentially
Resuscitation
1138–1143
adrenaline in cardiac arrest it remained impossible to change
distributed
the 82 (2011)
between the two study arms to be small.
decision not to participate. As a single centre study with approxiFinally, participation in the study by the SJA-WA paramedics
Contents lists is
availablewas
at ScienceDirect
mately 500 out of hospital cardiac arrests in which resuscitation
voluntary, hence only 40% of eligible patients were recruited.
commenced per year, it would not have been possible to reach the
We are unable to exclude the potential for selection bias, however
Resuscitation
required sample size. In addition it was not possible to continue
as
trial patients were well matched on baseline characteristics and
the study drugs reached their expiry date and no additional fundthere is no reason to suggest that paramedics who participated in
j o uadequate
r n a l h o m e sample
p a g e : w wsize
w . e l s e v i ethe
r . c otrial
m / l owere
c a t e / rmore
e s u s c ilikely
t a t i o n to selectively enroll patients into the trial.
ing was available. The failure to achieve an
left the trial underpowered to detect significant effects on survival
This study is unique in that it is the first randomised double blind
to hospital discharge.
placebo-controlled trial of adrenaline in cardiac arrest. To date the
Clinical paper
Second we were unable to assess the influence of CPR quality
evidence base underpinning this “standard of care” intervention
Effect ofadministration
adrenaline on
survival
in out-of-hospital
cardiac arrest:
randomised
or the timing of adrenaline
during
resuscitation
on
has been restricted
to animalAand
non-randomised clinical studies
Adrenalina
A randomised
mpson
double-blind placebo-controlled trial!
Ian G. Jacobs a,c,∗ , Judith C. Finn a,c , George A. Jelinek b , Harry F. Oxer c , Peter L. Thompson d,e
Table 2
of Emergency
University of Western Australia, 35 Stirling Highway, Crawley, 6009 Western Australia, Australia
receiving
placeboMedicine
versus(M516),
adrenaline.
Outcomes for patientsa Discipline
b
d,e
enaline (epinephrine) in treating
ndard of care for many decades.
nt survival to hospital discharge
d trial of adrenaline in out-ofine 1:1000 or placebo (sodium
ve 1 ml aliquots of the trial drug
ed included survival to hospital
ulation (ROSC) and neurological
period of which 601 underwent
s: 262 in the placebo group and
acteristics including age, gender
ving placebo and 64 (23.5%) who
arge occurred in 5 (1.9%) and 11
% CI 0.7–6.3). All but two patients
tatistically significant improveere was a significantly improved
Outcome
Department of Medicine, University of Melbourne (St Vincents Hospital), Victoria Parade, Fitzroy, 3065 Melbourne, Australia
St John Ambulance (Western Australia), PO Box 183, Belmont 6984, Western Australia, Australia
Placebo (n = 262), n (%)
Adrenaline (n = 272), n
School of Medicine and Population Health, University of Western Australia, Western Australia, Australia
e
Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, 6009 Western Australia, Australia
c
d
ROSC achieved pre-hospital
Admitted to hospital
Survived to hospital discharge
a r t i c l e
CPC 1 or 2
i n f o
22 (8.4%)
34 (13.0%)
5 (1.9%)
5 (100%)
a b s t r a c t
64 (23.5%)
69 (25.4%)
11 (4.0%)
9 (81.8%)
(%)
OR (95% CI)
p-Value
3.4 (2.0–5.6)
2.3 (1.4–3.6)
2.2 (0.7–6.3)
n/a
<0.001
<0.001
0.15
0.31
Article history:
Received 19 June 2011
Received in revised form 22 June 2011
Accepted 24 June 2011
Background: There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating
cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades.
Table 3
The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge
in out
of hospital cardiac
arrest.
non-shockable
initial
cardiac arrest rhythm.
Patient outcomes for adrenaline versus placebo by shockable and
Methods: We conducted a double blind randomised placebo-controlled trial of adrenaline in out-ofadrenaline 1:1000
or placebo (sodium
Shockable (n = 245)hospital cardiac arrest. Identical study vials containing either
Non-shockable
(n = 289)
Keywords:
chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug
Adrenaline
according
to current advanced
support
assessed includedAdrenaline
survival to hospital
Adrenaline
ORlife
(95%
CI) guidelines. Outcomes
Placebo
Out of hospital cardiac arrest Placebo
discharge (primary outcome),
pre-hospital return of spontaneous circulation (ROSC) and neurological
p-Value
Randomised controlled trial
outcome
(Cerebral
Performance
Category
Score
–
CPC).
Survival
Results:
A total of 4103 cardiac
were screened during
the study period of which32
601
underwent
Ambulance
5 (3.7%)
ROSC achieved pre-hospital
17 (13.5%)
32 (26.9%)
2.4arrests
(1.2–4.5)
(20.9%)
randomisation. Documentation
was available for a total of 534 patients: 262 in the placebo group and
p = 0.009
272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender
15 (11%)
19 (15.1%)
33 (27.7%)
2.2 (1.2–4.1)
36 (23.5%)
Admitted to hospital
and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who
p = 0.01
received adrenaline (OR = 3.4; 95% CI 2.0–5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11
5 (4.0%)
9 (7.6%)
2.0 (0.6–6.0)
(0%)
2 (1.3%)
Survived to hospital discharge
(4.0%)
patients receiving placebo
or adrenaline respectively0
(OR
= 2.2; 95% CI 0.7–6.3). All but
two patients
0.23
p =had
(both in the adrenaline group)
a CPC score of 1–2.
Conclusion: Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved
likelihood of achieving ROSC.
© 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
Cardiac arrest occurring out of hospital is a significant public
health issue with an estimated incidence in the United States of
95.7 per 100,000 person years.1,2 The overall case fatality varies
across different emergency medical services, but is mostly in
excess of 90% and has improved little over the last three decades.2
The routine use of adrenaline (epinephrine) in treating cardiac
arrest has been recommended for over half a century, being first
! A Spanish translated version of the abstract of this article appears as Appendix
in the final online version at doi:10.1016/j.resuscitation.2011.06.029.
∗ Corresponding author at: Discipline of Emergency Medicine (M516), University
of Western Australia, 35 Stirling Hwy, Crawley, 6009 Western Australia, Australia.
Tel.: +61 418 916 261.
E-mail address: [email protected] (I.G. Jacobs).
0300-9572/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.resuscitation.2011.06.029
described in 1906.3 The International Liaison Committee on Resuscitation (ILCOR) include adrenaline in their advanced life support
(ALS) resuscitation guidelines, despite there being no randomised
placebo-controlled trials in humans evaluating its efficacy in cardiac arrest.4 In 2010 ILCOR identified the need for randomised
clinical trials of vasopressor drugs in the treatment of cardiac
arrest.4
Animal studies have shown that adrenaline improves coronary
and cerebral perfusion.5 The survival outcomes in human studies (non randomised and observational) have been equivocal.6–9 A
meta-analysis of high dose versus standard dose adrenaline did not
include a comparison with no adrenaline and showed some benefit of high dose adrenaline on return of spontaneous circulation
(ROSC) but not survival to hospital discharge.10 In contrast, there
has been some concern regarding the potential harmful effects of
adrenaline on post cardiac arrest myocardial function and cerebral
microcirculation.11,12
OR (95% CI)
p-Value
6.9 (2.6–18.4)
p < 0.001
2.5 (1.3–4.8)
p = 0.005
n/a
Cuando usar...
• Uso precoz en PCR refractarios al shock
• USE la dosis correcta, NO megadosis.
• Masaje, masaje, ELECTRICIDAD
Vasopresina
• Secretada por la neuro-hipófisis
• Actúa en receptores V 1 endotelial
produciendo vasocontricción.
• No tiene efecto sobre miocardiocito.
journal of medicine
january 8 , 2004
established in 1812
vol. 350
no. 2
A Comparison of Vasopressin and Epinephrine for Out-of-Hospital
Cardiopulmonary Resuscitation
Volker Wenzel, M.D., Anette C. Krismer, M.D., H. Richard Arntz, M.D.,
Helmut Sitter, Ph.D., Karl H. Stadlbauer, M.D., and Karl H. Lindner, M.D.,
for the European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group*
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
abstract
original article
background
Vasopressin is an alternative to epinephrine for vasopressor therapy during cardiopul- From the Department of Anesthesiology
and Critical Care Medicine, Leopold-Franmonary resuscitation, but
clinical experience
withEpinephrine
this treatment has been
limited.
Vasopressin
and
vs. Epinephrine
zens University, Innsbruck, Austria (V.W.,
methods
K.H.S., K.H.L.); the Department of
Alone in Cardiopulmonary ResuscitationA.C.K.,
Medicine, Division of Cardiology–Pulmonol-
We randomly assigned adults
who had
had an out-of-hospital
cardiac arrest
toM.D.,
receive
Pierre-Yves
Gueugniaud,
M.D., Ph.D., Jean-Stéphane
David,
Ph.D.,ogy, Benjamin Franklin Medical Center, Free
Ericvasopressin
Chanzy, M.D.,orHervé
Ph.D., Pierre-Yves
Dubien,
M.D., University, Berlin, Germany (H.R.A.); and
two injections of either 40 IU of
1 mgHubert,
of epinephrine,
followed
by addithe Institute for Theoretical Surgery, PhilPatrick Mauriaucourt,
Bragança,
M.D.,was
Xavier
Billères,to
M.D.,
tional treatment with epinephrine
if needed.M.D.,
The Coralie
primary
end point
survival
ipps University, Marburg, Germany (H.S.).
Marie-Paule Clotteau-Lambert, M.D., Patrick Fuster, M.D., Didier Thiercelin, M.D.,
hospital admission, and theGuillaume
secondary
end
point
was
survival
to
hospital
discharge.
Debaty, M.D., Agnès Ricard-Hibon, M.D., Patrick Roux, M.D.,Address reprint requests to Dr. Lindner at
the Department of Anesthesiology and CritCatherine Espesson, M.D., Emgan Querellou, M.D., Laurent Ducros, M.D.,
Patrick Ecollan, M.D., Laurent Halbout, M.D., Dominique Savary, M.D.,ical Care Medicine, Leopold-Franzens University, Anichstr. 35, 6020 Innsbruck, AusA total of 1219 patients underwent
randomization;
33 were
excluded
miss-M.D.,
Frédéric Guillaumée,
M.D., Régine
Maupoint,
M.D.,because
Philippe of
Capelle,
tria, or at [email protected].
Cécile
M.D., Philippe
Dreyfus, M.D.,
Philippe
Nouguier,
ing study-drug codes. Among
the Bracq,
remaining
1186 patients,
589 were
assigned
to M.D.,
reAntoine
Gache,
M.D., Claude
Meurisse,
M.D., Bertrand
Boulanger,
M.D.,
*The investigators who participated in the
ceive vasopressin and 597 to
receive
epinephrine.
The
two treatment
groups
had simiClaude Lae, M.D., Jacques Metzger, M.D., Valérie Raphael, M.D.,
study group are listed in the Appendix.
lar clinical profiles. There Arielle
were Beruben,
no significant
differences
in
the
rates
of
hospital
M.D., Volker Wenzel, M.D., Comlavi Guinhouya, Ph.D.,
admission between the vasopressinChristian
group and
the epinephrine
group either
among
Vilhelm,
Ph.D., and Emmanuel
Marret,
M.D. pa- N Engl J Med 2004;350:105-13.
results
From Service d’Aide Médicale Urgente
2004 Massachusetts
tients with ventricular fibrillation (46.2 percent vs. 43.0 percent, P=0.48) or among Copyright ©(SAMU)
69, HospicesMedical
Civils deSociety.
Lyon, UniA BS T R AC T
versity of Lyon 1, Lyon (P.-Y.G., J.-S.D.);
those with pulseless electrical activity (33.7 percent vs. 30.5 percent, P=0.65). Among
SAMU 93, Bobigny (E.C.); Health Engineering Institute, University of Lille, Lille (H.H.,
patients with asystole,BACKGROUND
however, vasopressin use was associated with significantly
C.G., C.V.); Service Mobile d’Urgence et
the administration
of advanced
life in
support
for resuscitation from de Réanimation (SMUR), Edouard Herriot
higher rates of hospitalDuring
admission
(29.0 percent,
vs. 20.3cardiac
percent
the epinephrine
cardiac discharge
arrest, a combination
of vasopressin
and epinephrine
may Among
be more effective Hospital, Lyon (P.-Y.D.); SAMU 59, Lille
group; P=0.02) and hospital
(4.7 percent
vs. 1.5 percent,
P=0.04).
than epinephrine or vasopressin alone, but evidence is insufficient to make clinical (P.M.); SAMU 33, Bordeaux (C. Bragança);
732 patients in whom spontaneous
circulation was not restored with the two injections
Bataillon des Marins Pompiers, Marseille
recommendations.
(X.B.); SAMU 44, Nantes (M.-P.C.-L.);
of the study drug, additional
SMUR, Centre Hospitalier Universitaire
METHODStreatment with epinephrine resulted in significant imLyon-Sud, Lyon (P.F.); SAMU 06,
provement in the rates of
to hospital
admission
and hospital
discharge
in the
In asurvival
multicenter
study, we randomly
assigned
adults with
out-of-hospital
cardiac ar- (CHU)
Nice (D.T.); SAMU 38, Grenoble (G.D.);
receive
injections
of either
1 mg admission
of epinephrinerate,
and 40
IU of vaso- SMUR, Beaujon Hospital, Beaujon
vasopressin group, butrest
nottoin
the successive
epinephrine
group
(hospital
25.7
SAMU 31, Toulouse (P.R.);
pressin
or
1
mg
of
epinephrine
and
saline
placebo,
followed
by
administration
percent vs. 16.4 percent; P=0.002; hospital discharge rate, 6.2 percent vs. 1.7 percent; of the (A.R.-H.);
42, Saint-Etienne (C.E.); SAMU 29,
same combination of study drugs if spontaneous circulation was not restored and sub- SAMU
Brest (E.Q.); SMUR, CHU Lariboisière, Paris
P=0.002). Cerebral performance
was similar in the two groups.
sequently by additional epinephrine if needed. The primary end point was survival
conclusions
to hospital admission; the secondary end points were return of spontaneous circulation, survival to hospital discharge, good neurologic recovery, and 1-year survival.
(L.D.); SMUR, CHU Pitié–Salpêtrière, Paris
(P.E.); SAMU 14, Caen (L.H.); SAMU 74,
Annecy (D.S.); SMUR, Croix-Rousse Hos-
Vasopressin vs. Epinephrine in Out-of-Hospital
Cardiac Arrest
Vasopresina v/s adrenalina PCR- EH
Wenzel V et al. NEJM 2004; 350:105-13
1,186 patients
Vasopressin 40 units vs. epinephrine 1 mg IV q 3 min x 2 doses
If no ROSC, an additional 1 mg dose of epinephrine given at MD
discretion
•
•
Epinephrine (n= 597)
Vasopressin (n= 598)
1186 pacientes
Vasop 40 ui vs 1 mg
adrenalina cada 3
min x 2 dosis
25%
%
Discharged
ns
19%
20%
15%
18%
ns
10%
10%
9%
10%
ns
6%
5%
0%
p= .04
5%
2%
Overall
VF
PEA
Asystole
Vasopressin vs. Epinephrine in OutOut-ofof-Hospital
Cardiac Arrest
Wenzel V et al. NEJM 2004; 350:105350:105-13
1,186 patients
Vasopressin 40 units vs. epinephrine 1 mg IV q 3 min x 2 doses
If no ROSC, an additional 1 mg dose of epinephrine given at MD
discretion
Epinephrine (n= 597)
Vasopressin (n= 598)
Epinephrine vs. vasopressin
for in-hospital cardiac arrest
Adrenalina v/s vasopresina PCR IH
Stiell IG et al. Lancet 2001; 358:105-9
•
•
200 patients in
cardiac arrest
requiring drug
200therapy
pacientes en
PCREpi 1 mg vs.
vasopressin 40
Epi units
1 mgIVvs
vasopresina 40 ui
IV
Epinephrine
Vasopressin
75%
50%
ns
35%
39%
ns
25%
14%
12%
0%
1-hr survival
Discharged
Epinephrine vs. vasopressin
for in-hospital cardiac arrest
Stiell IG et al. Lancet 2001; 358:105358:105-9
200 patients in
cardiac arrest
requiring drug
therapy
Epi 1 mg vs.
Epinephrine
75%
50%
ns
39%
Vasopressin
Atropina
•
•
•
•
•
Trabajos de años 80
Revierte disminuciones FC, RVS y PA colinérgicas.
Util en bradicardia sinusal .
Se pensó de su utilidad en AESP y asistolía en base a
algunos reportes de casos
3 mg resulta en bloqueo vagal completo.
Atropina
•
•
•
Aumenta demanda miocárdica de oxígeno y puede iniciar
taquiarritmias.
Dosis < 0,5 mg pueden ser parasimpaticomiméticas.
Uso cuidadoso en SCA ó IAM.
Advance Publication by J-STAGE
Circulation Journal
Official Journal of the Japanese Circulation Society
http://www.j-circ.or.jp
Atropine Sulfate for Patients With Out-of-Hospital
Cardiac Arrest due to Asystole and
Pulseless Electrical Activity
The Survey of Survivors After Out-of-hospital Cardiac Arrest
in KANTO Area, Japan (SOS-KANTO) Study Group
Background: The 2005 guidelines for cardiopulmonary resuscitation (CPR) have recommended that administration of atropine can be considered for non-shockable rhythm, but there are insufficient data in humans.
•
• No debe ser utilizada de manera rutinaria
No mejora outcome neurológico
Methods and Results: The effects of atropine were assessed in 7,448 adults with non-shockable rhythm from
the SOS-KANTO study. The primary endpoint was a 30-day favorable neurological outcome after cardiac arrest.
In the 6,419 adults with asystole, the epinephrine with atropine group (n=1,378) had a significantly higher return
of spontaneous circulation (ROSC) rate than the epinephrine alone group (n=5,048) with an adjusted odds ratio
of 1.6 (95% confidence interval (CI) 1.4–1.7, P<0.0001), but the 2 groups had similar 30-day favorable neurological
outcome with an adjusted odds ratio of 0.6 (95%CI 0.2–1.7; P=0.37). In the 1,029 adults with pulseless electrical
activity (PEA), the 2 groups had similar rates of ROSC and 30-day favorable neurological outcome, and the epinephrine with atropine group had a significantly lower 30-day survival rate than the epinephrine alone group with
an adjusted odds ratio of 0.4 (95%CI 0.2–0.9, P=0.016).
en pacientes con PCR con ritmo no
desfibrilable.
Conclusions: Administration of atropine had no long-term neurological benefit in adults with out-of-hospital
cardiac arrest due to non-shockable rhythm. Atropine is not useful for adults with PEA.
• EN SUMA: ACLS 2010 no lo considera
Key Words:
Asystole; Atropine; Cardiac arrest; Neurological outcome; Pulseless electrical activity (PEA)
como parte de su algoritmo
C
ardiac arrest is a major public health problem in the
world. Recent guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care
have shown that basic CPR and early defibrillation are of
primary importance, and drug administration for advanced
cardiac life support (ALS) is of secondary importance during
cardiac arrest.1–3 There have been recent 2 clinical studies on
ALS in patients with out-of-hospital cardiac arrest. A multicenter, controlled clinical study by Stiel et al demonstrated
that standard ALS, which includes endotracheal intubation
and/or intravenous drug administration, does not improve
4
survival in humans. However, the use of atropine improves
short-term survival and is inexpensive and easy to administer.1 Literature to refute the use of atropine for asystole and
PEA is equally sparse and of limited quality.1 Asystole can
be precipitated or exacerbated by excessive vagal tone, and
administration of a vagolytic medication is consistent with a
physiologic approach.6 Moreover, recent CPR guidelines have
reported that administration of atropine remains a first line
drug for acute symptomatic bradycardia (Class 2a; weight of
evidence is in favorer of usefulness/efficacy). On the basis of
these findings, administration of atropine can be considered
Drogas utilizadas en RCP
• Vasopresores
• Antiarrítmicos
• Buffers
• Otras: Estrógenos, nitroprusiato, corticoides.
35
Antiarrítmicos
• Muchos efectos
• bloqueo canales de sodio
• bloqueo canales de potasio
• bloqueo canales de calcio
Principios Básicos
•
Antiarrítmicos no
mejoran sobrevida en
PCR.
•
Considerar efectos
arritmogénicos.
•
•
Interacciones entre AA
Evitar asociaciones de
AA.
•
Ojo con corazones
enfermos.
•
ICC mayor riesgo
arritmogénico
Potencial de acción...
0 – Canales de Na++
1 – Salida K+
2 – Entrada Ca++
3 – Cierre canales Ca++ +
Salida K+
Clasificación Vaughan
Williams
• Se basa en los canales iónicos bloqueados:
• Na+, K+ ó Ca++
• Efecto Beta bloqueador
• Efecto en la conducción y repolarización
Amiodarona
• Droga compleja con efectos en los canales
de Na+, K+ y Ca++,asi como propiedades de
bloqueo alfa y beta adrenórgico.
• Útil en arritmias auriculares y Ventriculares.
• Eficaz y con poco efecto arritmogénico
• Dilata las arterias coronarias y aumenta el
flujo coronario
Amiodarona
• Lo malo... Hipotensión y bradicardia
• Principalmente por vehículo y liberación de
histamina.
AMIODARONE FOR RESUSCITATION AF TER OUT- OF-HOSPITAL CARDIAC ARREST
AMIODARONE FOR RESUSCITATION AFTER OUT-OF-HOSPITAL CARDIAC
ARREST DUE TO VENTRICULAR FIBRILLATION
PETER J. KUDENCHUK, M.D., LEONARD A. COBB, M.D., MICHAEL K. COPASS, M.D., RICHARD O. CUMMINS, M.D.,
ALIDENE M. DOHERTY, B.S.N., C.C.R.N., CAROL E. FAHRENBRUCH, M.S.P.H., ALFRED P. HALLSTROM, PH.D.,
WILLIAM A. MURRAY, M.D., MICHELE OLSUFKA, B.S.N., AND THOMAS WALSH, M.I.C.P.
S
ARREST Trial
UDDEN death from cardiac causes, often
due to ventricular fibrillation, claims at least
Background Whether antiarrhythmic drugs im250,000 persons annually in the United
prove the rate of successful resuscitation after outStates.1,2 The American Heart Association
of-hospital cardiac arrest has not been determined in
randomized clinical trials.
guidelines for advanced cardiac life support state that
Methods We conducted a randomized, doubleantiarrhythmic medications are “acceptable, probably
blind, placebo-controlled study of intravenous amiohelpful” for the treatment of ventricular fibrillation
darone in patients withKudenchuk
out-of-hospital P
cardiac
or pulseless
tachycardia
et al.ar-N Engl
J Medventricular
1999; 341:871
-8that persists after
rest. Patients who had cardiac arrest with ventricular
three or more shocks from an external defibrillator
fibrillation (or pulseless ventricular tachycardia) and
(often called “shock-refractory” ventricular fibrillawho had not been resuscitated after receiving three
tion or tachycardia).3 This guarded recommendation
or more precordial shocks were randomly assigned
reflects the limited evidence supporting the use of
to receive 300 mg of intravenous amiodarone (246
Persistent
or
patients) or placebo (258 patients).
• Continue CPRthese agents, none of which have been convincingly
demonstrated to improve
the IV
success
attempted
VF/VT
Results recurrent
The treatment
groups had similar
clinical
• Epi 1 mg
q 3-5of
min
• Intubate
at once
resuscitation after cardiac arrest.4-6 We conducted a
profiles. There was no significant difference between
• Obtain IV access
the amiodarone and placebo groups in the mean
randomized clinical trial to determine the efficacy of
(±SD) duration of the resuscitation attempt (42±16
300 in
mg
intravenousAmio
amiodarone
patients Placebo
with out-of-hosand 43±16 minutes, respectively), the number of
pital cardiac arrest due to shock-refractory ventricular
shocks delivered (4±3 and 6±5), or the proportion
fibrillation or tachycardia.
of patients who required additional antiarrhythmic
• DF 360 J within 30-60 sec
ABSTRACT
drugs after the administration of the study drug (66
METHODS
percent and 73 percent). More patients in the amioThe study was conducted in Seattle and suburban King County,
darone group than in the placebo group had hypotenWashington. This region has more than 1.5 million residents and
sion (59 percent vs. 48 percent, P=0.04) or bradycardia
is served by 21 paramedic base stations and 15 hospitals, all of
(41 percent vs. 25 percent, P=0.004) after receiving
which participated in the trial. Seattle and King County have sim• IIb medications
the study drug. Recipients of amiodarone were more
ilar multitiered prehospital emergency-response
systems that follow
treatment protocols written in• accordance
with American Heart
likely to survive to be admitted to the hospital
Lidocaine
Association guidelines for advanced cardiac life support.7
(44 percent, vs. 34 percent of the placebo group;
• Bretylium
P=0.03). The benefit of amiodarone was consistent
• Mg sulfate
Protocol
• DF 360
30-60
secof
after
dose
among all subgroups
andJat
all times
drugmed
admin• Procainamide
Victims of cardiac arrest were
initially treated by fire-departistration. The adjusted
odds
ratio for survival
to admis• Pattern
“drug-shock”,
“drug-shock”
ment
personnel
(first
responders),
whobicarb)
initiated basic life-support
• (Na
sion to the hospital in the amiodarone group as commeasures, including the delivery of shocks by an automated expared with the placebo group was 1.6 (95 percent
ternal defibrillator. When paramedics arrived, they provided adconfidence interval, 1.1 to 2.4; P=0.02). The trial did
vanced life-support measures. Adults with nontraumatic out-ofnot have sufficient statistical power to detect differhospital cardiac arrest were eligible for inclusion in the study if
ences in survival to hospital discharge, which difventricular fibrillation or pulseless ventricular tachycardia (on inifered only slightly between the two groups.
tial presentation or any time in the course of the resuscitation atConclusions In patients with out-of-hospital carditempt) was present after three or more precordial shocks had been
ARREST Trial
Trial
Arrest
Kudenchuk P et al. N Engl J Med 1999; 341:871-8
N= 504
70%
60%
50%
Survival to 40%
Admission
64%
p= .03
49%
44%
41%
39%
34%
30%
38%
33%
17%
20%
12%
10%
0%
All
patients
VF
Asys or
PEA
ROSC
No ROSC
dispatch log sheets, and hospital charts (for admitted patients).
•
Patients surviving to hospital admission were followed for
functional status at discharge as part of the study procedure;
however, results are not yet available.
Alive Trial
Study Protocol
Figure 1
Patients with VF
= VF persists
or recurs
3 Unsuccessful defibrillation attempts
IV epinephrine
Fourth defibrillation shock
RANDOMIZATION
IV amiodarone 5 mg/kg AND IV lidocaine placebo
IV lidocaine 1.5 mg/kg AND IV amiodarone placebo
Fifth defibrillation shock
Fifth defibrillation shock
Second infusion of amiodarone (2.5 mg/kg)
Second infusion of lidocaine (1.5 mg/kg)
Further shocks
Further shocks
Epinephrine infusion at 5-min intervals
Epinephrine infusion at 5-min intervals
Data from Dorian et al.3
ALIVE Trial
Dorian P et al. NEJM; 346:884346:884-90
N= 348
Amio vs. Lido
ALIVE Trial
Dorian P et al. NEJM; 346:884-90
Alive Trial
N= 348
Amio vs. Lido
Toronto EMS
911-1st DF = 12 + 7 min
911-drug = 25 + 8 min
25%
•n= 345
•Toronto EMS
20%
Admission
23%
p< .004
15%
10%
11%
5%
0%
Amio
Lido
•Sobrevida a la
admisión
ALIVE Trial
Dorian P et al. NEJM; 346:884346:884-90
N= 348
Amio vs. Lido
Toronto EMS
911911-1st DF = 12 + 7 min
911911-drug = 25 + 8 min
Ojo con Amiodarona
bradicardizantes y vasodilatadores:
• Efectos
cuidado en ptes inestables.
cree que es por efecto de dilución quiza
• Se
por liberación de histamina.
• Nivel de evidencia AHA en PCR:
• Grado de recomendación: II B
B
Procainamide and Survival in Ventricular
Fibrillation Out-of-hospital Cardiac Arrest
David T. Markel, Laura S. Gold, MSPH, Judith Allen, MPH, Carol E. Fahrenbruch, MSPH, Thomas D.
Rea, MD, MPH, Mickey S. Eisenberg, MD, PhD, and Peter J. Kudenchuk, MD
Abstract
Objectives: Procainamide is an antiarrhythmic drug of unproven efficacy in cardiac arrest. The association between procainamide and survival from out-of-hospital cardiac arrest was investigated to better
determine the drug’s potential role in resuscitation.
• Estuvo en guidelines 2000
• 2005 fue eliminada por convivencia
• Estudio que demostró sobrevida
• VWAIa
• Efectos vasodilatador
• Guidelines actuales avala su uso en FAMethods: The authors conducted a 10-year study of all witnessed, out-of-hospital, ventricular fibrillation
(VF) or pulseless ventricular tachycardia (VT) cardiac arrests treated by emergency medical services
(EMS) in King County, Washington. Patients were considered eligible for procainamide if they received
more than three defibrillation shocks and intravenous (IV) bolus lidocaine. Four logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) describing the relationship
between procainamide and survival.
Results: Of the 665 eligible patients, 176 received procainamide, and 489 did not. On average, procainamide recipients received more shocks and pharmacologic interventions and had lengthier resuscitations. Adjusted for their clinical and resuscitation characteristics, procainamide recipients had a lower
likelihood of survival to hospital discharge (OR = 0.52; 95% CI = 0.36 to 0.75). Further adjustment for
receipt of other cardiac medications during resuscitation negated this apparent adverse association
(OR = 1.02; 95% CI = 0.66 to 1.57).
Conclusions: In this observational study of out-of-hospital VF and pulseless VT arrest, procainamide as
second-line antiarrhythmic treatment was not associated with survival in models attempting to best
account for confounding. The results suggest that procainamide, as administered in this investigation,
does not have a large impact on outcome, but cannot eliminate the possibility of a smaller, clinically relevant effect on survival.
ACADEMIC EMERGENCY MEDICINE 2010; 17:617–623 ª 2010 by the Society for Academic Emergency
Medicine
Keywords: antiarrhythmia agents, arrhythmia, cardiopulmonary resuscitation, survival
ntiarrhythmic medications are frequently during resuscitation from cardiac arrest, although
research supporting their efficacy in this setting
is scarce.1–4 Supporting evidence is stronger for their use
in the treatment of hemodynamically stable arrhythmias,5 which, along with encouraging results from some
animal studies,6 has spurred the extension of their use to
From the University of Washington School of Medicine (DTM),
Seattle, WA; Division of Emergency Medical Services, Public
Health Seattle and King County (DTM, LSG, JA, CEF, TDR,
MSE, PJK), Seattle, WA; the Department of Epidemiology, University of Washington School of Public Health (LSG), Seattle,
WA; the Department of Medicine, University of Washington
School of Medicine (TDR, MSE), Seattle, WA; and the Department of Medicine, Division of Cardiology, University of Washington School of Medicine (PJK), Seattle, WA.
Received August 9, 2009; revisions received September 11 and
November 8, 2009; accepted December 6, 2009.
Address for correspondence and reprints: Peter J. Kudenchuk,
MD; e-mail: [email protected].
the resuscitation of hemodynamically unstable cardiac
arrest in humans. Antiarrhythmic agents currently recommended by the American Heart Association (AHA)
for the treatment of cardiac arrest include amiodarone,
lidocaine, and magnesium.4
Procainamide is a Vaughn Williams Class IA antiarrhythmic with conduction-slowing and vasodilatory
properties. Currently, the AHA recommends procainamide for hemodynamically stable ventricular arrhythmias and atrial arrhythmias in patients with preserved
ventricular function, but makes no recommendations
about the use of the drug for the treatment of cardiac
arrest.4 Indeed, the sum of the world’s published experience with intravenous (IV) procainamide in cardiac
arrest is limited to the reporting of outcomes in a subgroup of only 20 patients from a larger observational
study7 and no randomized clinical trials.
For patients with cardiac arrest in whom defibrillation or first-line cardiac medications are unsuccessful,
alternative treatments are limited. A better understanding of alternative treatments such as procainamide may
Flutter y TV estable, no PCR
ª 2010 by the Society for Academic Emergency Medicine
doi: 10.1111/j.1553-2712.2010.00763.x
ISSN 1069-6563
PII ISSN 1069-6563583
617
Procainamide and Survival in Ventricular
Fibrillation Out-of-hospital Cardiac Arrest
David T. Markel, Laura S. Gold, MSPH, Judith Allen, MPH, Carol E. Fahrenbruch, MSPH, Thomas D.
Rea, MD, MPH, Mickey S. Eisenberg, MD, PhD, and Peter J. Kudenchuk, MD
620
Abstract
Markel et al.
•
PROCAINAMIDE IN CARDIAC ARREST
Objectives: Procainamide is an antiarrhythmic drug of unproven efficacy in cardiac arrest. The association between procainamide and survival from out-of-hospital cardiac arrest was investigated to better
determine the drug’s potential role in resuscitation.
Table 1
Baseline Characteristics of the
665 The
Study
Patients
Methods:
authors
conducted a 10-year study of all witnessed, out-of-hospital, ventricular fibrillation
(VF) or pulseless ventricular tachycardia (VT) cardiac arrests treated by emergency medical services
(EMS) in King County, Washington. Patients were considered eligible for procainamide if they received
more than three defibrillation shocks and intravenous (IV) bolus lidocaine. Four logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) describing the relationship
All Procainamide Recipients
between procainamide and survival.
Characteristic
Patients Not Treated With
Procainamide
(n = 489)
(n = and
176)
Results: Of the 665 eligible patients, 176 received procainamide,
489 did not. On average, procainamide recipients received more shocks and pharmacologic interventions and had lengthier resuscitamedian
(n)
63.0 (±12.5),
63.0procainamide recipients had a lower63.7
tions. Adjusted
for their clinical and resuscitation
characteristics,
likelihood of survival to hospital discharge62.7
(OR = (±12.7),
0.52; 95% CI
= 0.36
to 0.75). Further adjustment for63.5
63.0
(152)
receipt of other cardiac medications during resuscitation negated this apparent adverse association
64.9
(±11.5),
64.0
(24)
64.7
(OR = 1.02; 95% CI = 0.66 to 1.57).
Age (yr), mean (±SD),
(±13.9), 64.0
Males
(±13.8), 64.0 (388)
Females
(±14.7), 65.0 (101)
Male sex, n (% of group) Conclusions: In this observational study of
152
(86.4)
388 (79.3)
out-of-hospital VF and pulseless VT arrest, procainamide as
Arrest in public, n (% of group)
174 (35.6)
second-line antiarrhythmic treatment was 62
not (35.2)
associated with survival in models attempting to best
account for confounding. The results suggest
procainamide, as administered in this investigation,
Bystander CPR, n (% of group)
112 that
(63.6)
338 (69.1)
does not have a large impact on outcome, but cannot eliminate the possibility of a smaller, clinically releContinuous variables, mean
(±SD), median
vant effect on survival.
Dispatch to arrival of first
EMS unit
4.9 (±2.2), 5.0 (valid n = 161)
4.8 (±2.0), 4.8 (valid n = 453)
ACADEMIC EMERGENCY MEDICINE 2010; 17:617–623 ª 2010 by the Society for Academic Emergency
(BLS or ALS) (minutes)Medicine
Dispatch to ALS arrival (minutes)
8.3 cardiopulmonary
(±3.6), 8.0 (valid
n = 176)
8.5 (±3.7), 8.0 (valid n = 461)
Keywords: antiarrhythmia agents, arrhythmia,
resuscitation,
survival
Total number of shocks (BLS and ALS)
12.4 (±6.6), 10.0
7.0 (±3.2), 6.0
Estimated length of resuscitation (minutes)*
47.3 (±15.9), 46.9 (valid n = 149)
38.5 (±13.3), 37.5 (valid n = 423)
EMS interventions, n (% ntiarrhythmic
of group) medications are frequently dur- the resuscitation of hemodynamically unstable cardiac
arrest in humans. Antiarrhythmic agents currently
recing resuscitation from cardiac arrest, although
Epinephrine
174 (98.9)
415 (84.9)
ommended by the American Heart Association
(AHA)
research supporting their efficacy in this setting
Magnesium
58 (33.0)
49 (10.0)
1–4
is scarce. Supporting evidence is stronger for their use for the treatment of cardiac arrest include amiodarone,
Bretylium
30 (17.0)
26 (5.3)
in the treatment of hemodynamically stable arrhyth- lidocaine, and magnesium.4
5
Medication dosages
(mg),
mean
medianresults
(n) from some
mias,
which,
along (±SD),
with encouraging
Procainamide is a Vaughn Williams Class IA antiarEpinephrine (mg)
6.8to(±4.2),
6.0 with
(174)conduction-slowing and vasodilatory
4.4 (±3.2), 4.0 (414)
animal studies,6 has spurred the extension of their use
rhythmic
properties.
Currently,
procainLidocaine (mg)
266.5 (±67.5),
300.0
(175) the AHA recommends
189.0
(±79.0), 200.0 (488)
amide 2.0
for (58)
hemodynamically stable ventricular2.7
arrhythMagnesium (g) From the University of Washington School of Medicine (DTM),
2.6 (±1.4),
(±1.9), 2.0 (49)
Seattle, WA; Division of Emergency Medical Services, Public mias and atrial arrhythmias in patients with preserved
Bretylium (mg)!Health Seattle and King County (DTM, LSG, JA, CEF,
870.0
(±481.5), 950.0 (30)
692.3 (±376.2), 500.0 (26)
TDR, ventricular function, but makes no recommendations
Procainamide (mg)
742.9
about the500.0
use of the drug for the treatment —
of cardiac
MSE, PJK), Seattle, WA; the Department of Epidemiology,
Uni-(±341.6),
versity
Outcomes, number
(% of
ofWashington
group) School of Public Health (LSG), Seattle, arrest.4 Indeed, the sum of the world’s published experience with intravenous (IV) procainamide305
in cardiac
WA;
the Department of Medicine, University of Washington
Admitted alive to
hospital
80 (45.5)
(62.4)
School of Medicine (TDR, MSE), Seattle, WA; and the Depart- arrest is limited to the reporting of outcomes in a subSurvived to hospital
discharge
33
(18.8)
1
56
(31.9)
group of only 20 patients from a larger observational
ment of Medicine, Division of Cardiology, University of Wash-
A
ington School of Medicine (PJK), Seattle, WA.
study7 and no randomized clinical trials.
For patients with resuscitation;
cardiac arrest in EMS
whom =
defibrillaReceived
August BLS
9, 2009;
received
September
11 and
ALS = advanced life
support;
= revisions
basic life
support;
CPR
= cardiopulmonary
emergency medical services.
tion or first-line cardiac medications are unsuccessful,
8, 2009; accepted December 6, 2009.
*Calculated as theNovember
interval
between
arrival
of
first
EMS
personnel
and
the
final
time
recorded
in
the prehospital record when
Address for correspondence and reprints: Peter J. Kudenchuk, alternative treatments are limited. A better understandresuscitation efforts
and ⁄ or the patient was readied for ing
transport
to hospital.
of alternative
treatments such as procainamide may
MD;ceased
e-mail: [email protected].
!Bretylium was removed from resuscitation guidelines beginning January 1, 2001; 56 patients were treated with bretylium prior
to this date, 30 of whom also received procainamide and 26 of whom did not.
ª 2010 by the Society for Academic Emergency Medicine
doi: 10.1111/j.1553-2712.2010.00763.x
ISSN 1069-6563
PII ISSN 1069-6563583
617
Drogas utilizadas en RCP
• Vasopresores
• Antiarrítmicos
• Buffers
• Otras: Estrógenos, nitroprusiato, corticoides.
51
Bicarbonato de sodio
• Desde las guidelines de 1986 que NO está
recomendado.
• “ Puede ser utilizado a discreción del líder
del equipo”
• No hay buen nivel de evidencia para estos
estudios.
• Conductas pendulares
Resuscitation 54 (2002) 47 !/55
www.elsevier.com/locate/resuscitation
Clinical use of sodium bicarbonate during cardiopulmonary
resuscitation* is it used sensibly?!
/
Gad Bar-Joseph a,c,*, Norman S. Abramson a, Linda Jansen-McWilliams b, Sheryl
F. Kelsey b, Tatiania Mashiach d, Mary T. Craig a, Peter Safar a, Brain Resuscitation
Clinical Trial III (BRCT III) Study Group
a
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15260, USA
b
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15260, USA
Pediatric Intensive Care Unit, Rambam Medical Center and the Bruce Rappaport Faculty of Medicine, Technion */Israel Institute of Technology,
Haifa 31096, Israel
d
Quality Assurance Department, Rambam Medical Center and the Bruce Rappaport Faculty of Medicine, Technion */Israel Institute of Technology,
Haifa 31096, Israel
c
• Se dieron cuenta con este registro que BS
Received 27 August 2001; received in revised form 21 January 2002; accepted 21 January 2002
era utilizado un 55% de las reanimaciones
de PCR.
Abstract
This study retrospectively analyzed the pattern of sodium bicarbonate (SB) use during cardiopulmonary resuscitation (CPR) in
the Brain Resuscitation Clinical Trial III (BRCT III). BRCT III was a prospective clinical trial, which compared high-dose to
standard-dose epinephrine during CPR. SB use was left optional in the study protocol. Records of 2915 patients were reviewed.
Percentage, timing and dosage of SB administration were correlated with demographic and cardiac arrest variables and with times
from collapse to Basic Life Support, to Advanced Cardiac Life Support (ACLS) and to the major interventions performed during
CPR. SB was administered in 54.5% of the resuscitations. The rate of SB use decreased with increasing patient age */primarily
reflecting shorter CPR attempts. Mean time intervals from arrest, from start of ACLS and from first epinephrine to administration
of the first SB were 299/16, 199/13, and 10.89/11.1 min, respectively. No correlation was found between the rate of SB use and the
pre-ACLS hypoxia times. On the other hand, a direct linear correlation was found between the rate of SB use and the duration of
ACLS. We conclude that when SB was used, the time from initiation of ACLS to administration of its first dose was long and severe
metabolic acidosis probably already existed at this point. Therefore, if SB is used, earlier administration may be considered.
Contrary to physiological rationale, clinical decisions regarding SB use did not seem to take into consideration the duration of preACLS hypoxia times. We suggest that guidelines for SB use during CPR should emphasize the importance of pre-ACLS hypoxia
time in contributing to metabolic acidosis and should be more specific in defining the duration of ‘protracted CPR or long
resuscitative efforts’, the most frequent indication for SB administration. # 2002 Elsevier Science Ireland Ltd. All rights reserved.
• 2915 pacientes
• Conclusión: enfatizan en intentar estimar
Keywords: Acid !/base; Acidosis; Bicarbonate; Sodium bicarbonate; Buffer therapy; Cardiac arrest; Cardiopulmonary resuscitation; Advanced life
support
tiempos de PCR. En estadíos precoces de
acidosis, podría ser útil
1. Introduction
Excessive lactate production always results from
tissue hypoxia and anaerobic metabolism. Since severe
!
Presented in part at the 7th World Congress of Intensive and
Critical Care Medicine, Ottawa, Canada, July 1997.
* Corresponding author. Tel.: "/972-4-8542855/9834948; fax: "/9724-8542864
E-mail address: [email protected] (G. BarJoseph).
metabolic acidosis was considered detrimental during
cardiopulmonary resuscitation (CPR), buffering with
sodium bicarbonate (SB) was intuitively and empirically
included in its initial pharmacological armamentarium
[1]. SB was subsequently recommended as a first line
drug in the first American Heart Association’s (AHA)
Standards for Cardiopulmonary Resuscitation and
Advanced Cardiac Life Support (ACLS) [2]. Its use
was re-evaluated in the 1986 update of the ACLS
Guidelines, where it was no longer recommended, but
rather ‘could be used at the discretion of the team
0300-9572/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 0 0 - 9 5 7 2 ( 0 2 ) 0 0 0 4 5 - X
Bicarbonato de sodio
Grado de recomendación AHA: Nivel III
Considerar en situaciones especiales:
Acidosis severa
Bloqueadores canales de Sodio
Hiperkalemia
Drogas utilizadas en RCP
• Vasopresores
• Antiarrítmicos
• Buffers
• Otras: magnesio,nitroprusiato, estrógenos,
aminofilina.
55
Magnesio
•
•
Cofactor para la utilización celular de ATP
•
•
•
PCR: Podría ayudar. Uso de rutina no es útil.
Deficiencia de Mg++ se asocia a arritmias, ICC y muerte
súbita.
Evidencia basado en reportes de casos
Estudio MAGIC
Magnesio
•
Dosis: Carga 1 a 2 g (8-16mEq) diluido en 50 a 100 ml
sg5% en 5 a 60’. Infusion de 0,5-1 g/h.
•
•
En emergencias 1-2g en 10 ml a pasar en 2 min.
•
•
Relacionado a embarazo.
Efectivo y droga de elección en manejo de Torsade de
Pointes (Sindromes de QT largo).
Grado de recomendación: IIb ( torsade)
Concepto de post
acondicionamiento isquémico
Prolonged CPR Hemodynamic study
SNPeCPR
(8 animals)
25 min
If ROSC
8 min
of untreated VF
S-CPR
(8 animals)
“eCPR” NO SNP
(8 animals)
Yannopoulos, Matsuura, Schultz, et al.
Crit Care Med. 2011 Feb 24.
24-hour
survival
Carotid Blood Flow (ml/min)
350
SNPeCPR
S-CPR +epi
ACD CPR+ITD+AB
300
250
200
†*
†*
150
†*
100
*
*
50
*
†*
†*
*
*
0
Baseline
5m
10m
15m
CPR
20m
25m
End-tidal CO2(mmHg)
40
SNPeCPR
35
S-CPR+ epi ETCO2
ACD CPR+ITD+AB
30
25
†*
†*
†*
20
†*
†*
15
*
10
*
*
5
*
*
0
Baseline
5m
10m
15m
CPR
20m
25m
24 Hour Overall Performance Category Score
5
(dead)
*
*
4
3
Good neurological
outcomes
2
1
SNPeCPR
eCPR
S-CPR
Background Endogenous adenosine might cause or perpetuate bradyasystole. Our aim was to determine whether
aminophylline, an adenosine antagonist, increases the rate of return of spontaneous circulation (ROSC) after out-ofhospital cardiac arrest.
Lancet 2006; 367: 1577–
University of British Col
Vancouver, BC, Canada
(R B Abu-Laban MD,
C M McIntyre MD,
Methods In a double-blind trial, we randomly assigned 971 patients older than 16 years with asystole or pulseless Prof J M Christenson MD,
electrical activity at fewer than 60 beats per minute, and who were unresponsive to initial treatment with epinephrine C A van Beek BSN,
and atropine, to receive intravenous aminophylline (250 mg, and an additional 250 mg if necessary) (n=486) or Prof G D Innes MD,
Riyad B Abu-Laban,
Caroline M McIntyre,
James M Christenson,
Catherina
A van2001
Beek, Grant
Innes, Robin K O’Brien,
Karen
P Wanger,
placebo (n=485).
The patients
were enrolled
between
January,
andD September,
2003,
from
1886 people who had R K O’Brien PharmD,
K P Wanger MD,
R Douglas McKnight, Kenneth G Gin, Peter J Zed, Jeffrey Watts, Joe Puskaric, Iain A MacPhail, Ross G Berringer, Ruth A Milner
had cardiac arrests. Standard resuscitation measures were used for at least 10 mins after the study drug was R D McKnight MD, K G Gin
administered.
Analysis was by intention-to-treat. This trial is registered with the ClinicalTrials.gov registry with the P J Zed PharmD, I A MacPh
Summary
R G Berringer MD,
number NCT00312273.
Background Endogenous adenosine might cause or perpetuate bradyasystole. Our aim was to determine whether Lancet 2006; 367: 1577–84
A Milner MSc); British
aminophylline, an adenosine antagonist, increases the rate of return of spontaneous circulation (ROSC) after out-of- University of BritishRColumbia,
Columbia
Ambulance Se
Vancouver,
BC,
Canada
cardiac
arrest.
Findings hospital
Baseline
characteristics
and survival predictors were similar in both groups. The median time from
theMD,Victoria, BC, Canada
(R B Abu-Laban
C M McIntyreof
MD, (J M Christenson,
arrival ofMethods
the advanced
life-support
to 971
study
drugolder
administration
was asystole
13 min.
proportion
In a double-blind
trial, paramedic
we randomly team
assigned
patients
than 16 years with
or The
pulseless
Prof J M Christenson MD,
K P Wanger, J Watts EMApatients who
hadactivity
an ROSC
wasthan
24·5%
in the
aminophylline
group
and 23·7%
in thetreatment
placebowith
group
(difference
0·8%;
electrical
at fewer
60 beats
per minute,
and who were
unresponsive
to initial
epinephrine
C A van
Beek BSN,
J Puskaric EMA-3); and Ce
Prof G Ddrug
Innes MD,
and atropine,
to receive
intravenous
(250
mg, andwith
an additional
250 tachyarrhythmias
mg if necessary) (n=486)
95% CI –4·6%
to 6·2%;
p=0·778).
Theaminophylline
proportion of
patients
non-sinus
afterorstudy
R K O’Brien PharmD,for Clinical Epidemiolog
placebowas
(n=485).
The in
patients
were enrolled between
2001 and
September,
from
1886 peopleSurvival
who had to hospital
administration
34·6%
the aminophylline
groupJanuary,
and 26·2%
in the
placebo2003,
group
(p=0·004).
K P Wanger MD,
Evaluation, Vancouver, B
had cardiac arrests. Standard resuscitation measures were used for at least 10 mins after the study drug was R D McKnight MD, K G Gin MD,
admission
and survival to hospital discharge were not significantly different between the groups. A multivariate Canada (R B Abu-Laban,
administered. Analysis was by intention-to-treat. This trial is registered with the ClinicalTrials.gov registry with the P J Zed PharmD, I A MacPhail
MD,
C A van Beek, R A Milner)
logistic regression analysis showed no evidence of a significant subgroup or interactive effect from aminophylline.
Aminophylline in bradyasystolic cardiac arrest: a randomised
placebo-controlled trial
R G Berringer MD,
R A Milner MSc); British
Correspondence to:
Columbia Ambulance
DrService,
Riyad B Abu-Laban,
Victoria, BC, Canada
Department of Emergenc
(J M Christenson,
Medicine, Vancouver Gen
K P Wanger, J Watts EMA-3,
Hospital,
J Puskaric EMA-3); and
Centre Vancouver,
for Clinical Epidemiology
and
BC V5Z
1M9, Canada
Evaluation, Vancouver,
BC,
abulaban@interchange.
Canada (R B Abu-Laban,
C A van Beek, R A Milner)
number NCT00312273.
FindingsAlthough
Baseline characteristics
and survival
predictors
were similar
in both groups. The
the
Interpretation
aminophylline
increases
non-sinus
tachyarrhythmias,
wemedian
notedtime
no from
evidence
that it
arrival
of
the
advanced
life-support
paramedic
team
to
study
drug
administration
was
13
min.
The
proportion
of
significantly increases the proportion of patients who achieve ROSC after bradyasystolic cardiac arrest.
patients who had an ROSC was 24·5% in the aminophylline group and 23·7% in the placebo group (difference 0·8%;
95% CI –4·6% to 6·2%; p=0·778). The proportion of patients with16–24
non-sinus tachyarrhythmias after study drug
arrest.
Introduction
We undertook
this study
to to
assess
the effect of
administration was 34·6% in the aminophylline group and 26·2% in the placebo
group (p=0·004).
Survival
hospital
aminophylline
during
cardiopulmonary
resuscitation
Out-of-hospital
sudden
cardiac
arrest
treated
by
admission and survival to hospital discharge were not significantly different between the groups. A multivariate
logistic
regression
analysis
no evidence
of a significant
subgroup
interactivewith
effect out-of-hospital
from aminophylline.
(CPR)
of orpatients
bradyasystolic
emergency
medical
services
hasshowed
an estimated
incidence
Correspondence to:
of 55 per 100 000 person-years, which translates to about cardiac arrest unresponsive to initial therapy. Dr Riyad B Abu-Laban,
Interpretation Although aminophylline
increases non-sinus tachyarrhythmias, we noted no evidence that it Department of Emergency
155 000 episodes
annually in the USA.1 Bradyasystole is
significantly increases the proportion of patients who achieve ROSC after bradyasystolic cardiac arrest.
Medicine, Vancouver General
the first recorded rhythm in up to 52% of cardiac arrests, Methods
Hospital, Vancouver,
16–24
1M9,3,
Canada
and manyIntroduction
additional patients with an initial cardiac arrest arrest.
We undertook
this
trial
between
Jan
21,
2001,
and
Sept
We undertook this study to assess the effect of BC V5Z
[email protected]
during
cardiopulmonary
resuscitation
sudden
cardiac arrest
treated by
rhythm Out-of-hospital
of ventricular
fibrillation
deteriorate
to aminophylline
2003, at eight
advanced
life-support
paramedic stations
(CPR)
of
patients
with
out-of-hospital
bradyasystolic
emergency
medical
services
has
an
estimated
incidence
2,3
bradyasystole after defibrillation efforts. Fewer than 3% in the greater Vancouver and Chilliwack region in
of 55 per 100 000 person-years, which translates to about cardiac arrest unresponsive to initial therapy.
Canada. This region has a population of more than two
of patients
presenting
with bradyasystole
survive to
155 000
episodes annually
in the USA.1 Bradyasystole
is
hospital discharge;
however,
more
17%
of all cardiac
million, served by the British Columbia Ambulance
the first recorded
rhythm
in upthan
to 52%
of cardiac
arrests, Methods
4
and manyhad
additional
with an initial
cardiac
arresta We
undertook
this trial between
Jan 21,arrest
2001, and
Sept 3,are treated
arrest survivors
initialpatients
bradyasystole.
Thus,
even
Service.
Out-of-hospital
cardiac
patients
rhythm
of
ventricular
fi
brillation
deteriorate
to
2003,
at
eight
advanced
life-support
paramedic
stations
small improvement in survival from 2,3bradyasystolic by paramedics with protocols based on American Heart
bradyasystole after defibrillation efforts. Fewer than 3% in the greater Vancouver and
Chilliwack region in
cardiac arrest
could save thousands of lives.
Association guidelines,25 and
are not taken to hospital
of patients presenting with bradyasystole survive to Canada. This region has a population of more than two
Adenosine
is discharge;
an endogenous
purine
that million,
unless served
a perfusing
develops,Ambulance
a shockable rhythm
hospital
however, more
thannucleoside
17% of all cardiac
by the rhythm
British Columbia
4
depressesarrest
the survivors
sinoatrial
blocks atrioventricular
persists,
or there are
extenuating
circumstances
such as
had node,
initial bradyasystole.
Thus, even a Service.
Out-of-hospital
cardiac
arrest patients
are treated
smallinhibits
improvement
in survivalactivity
from bradyasystolic
paramedics with
protocols based on
American
Heart
conduction,
the pacemaker
of the His- byhypothermia
or intermittently
palpable
pulses.
25
gen may not only have a direct developed by reviewing some of the pertherapeutic benefit in some instances, tinent clinical observations, extensive exestrogen administration may also be perimental data, and the related safety
synergistic with other resuscitative in- and feasibility of this treatment. The disRationale (10,
for 18,
routine
immediate
administration
of intravenous
will also detail
some of the curterventions
19, 22,and
27–29,
32). cussion
rent scientific
estrogen
for all
critically
ill and
patients initiatives related to sex
A significant
body
of laboratory
evi-injured
dence, bridging across a variety of species hormone therapy, and it will provide recommendations
for future research in
Jane aG. breadth
Wigginton, MD;
Paul E. Pepe, MD; models,
Ahamed H. Idris,
MD
and
of experimental
nowIn addition
supports
the concept that estrogen what is now being called resuscitative
to a number of very compelling clinical obser- efit is profound. Even if estrogen only changes the outcome in
endocrinology.
vations,
extensive
body of therapeutic
extremely supportive
experimen- a relatively small percentage of applicable cases, the potential
may
beanan
effective
intervental data has generated a very persuasive argument that intra- impact may still be of dramatic proportions in terms of the
of Internal Medicine (PEP, tion
for
a spectrum
of severe
physiologic
venous
estrogen
should be routinely
administered,
as soon as absolute number of lives saved and the resources spared
edicine) (PEP, JGW, AHI), insults
Cohort
studies
of sex
hormone
possible, toand
all persons
identified
as
having
a
critical
illness or worldwide.
Resources
may be spared
not only
in terms of
injuries (12–28). Although
injury. Although, to date, definitive gold-standard clinical trials diminishing the economic impact of death and long-term disof Public Health (PEP), The
influences
resuscitation
clinical
trials
are stillargument
lacking,
are lacking, what
has made
this provocative
even ability,
but also in termsin
of preventing
extended intensive care
stern Medical Center and definitive
more convincing is the longstanding, documented safety of unit stays and treatment of preventable complications that
striking
experimental
spital System, Dallas TX; the
intravenous
estrogen
for various illnessesevidence,
and conditions as
as result in
longer recovery.
(Crit Care Medand
2010;Cardiac
38[Suppl.]:ArFemale
Sex Hormones
Sex,
Drugs
and
R&R
(Reanimation
&
Resuscitation):
well as
the
relative
ease
and
inexpensive
cost
of
treatment.
As
S620
–S629)
Center for Resuscitation well
as several compelling clinical obser- rest. In the mid-1990s there was an existsuch,
even routine prehospital
administration becomes exKEY WORDS: resuscitation; cardiopulmonary resuscitation; carDallas, TX. Sex Hormone
Interventions
in Resuscitation
vations
haveforspawned
a very More
convincing
arrest;
hemorrhagic shock;
trauma; traumatic
brain injury;
tremely feasible
a myriad of conditions.
importantly, diac
ing
controversy
regarding
women
having
ational Institutes of Health
the worldwide magnitude of potential patients who could ben- burns; estrogen; progesterone; antiapoptotic; anti-inflammatory
argument
that
intravenous
(IV)
estrogen,
cience Award grant numworse outcomes than men in heart attack
and
perhaps
other
female
sex
hormones
JJaannee G
.
W
i
g
g
i
n
t
o
n
,
M
D
,
F
A
C
E
P
G. Wigginton, MD, FACEP
and stroke (5– 8, 37– 40). It was argued,
ver the last several decades, effects in numerous conditions ranging conditions over the past several decades
t off-label uses
of
estro(such
progesterone),
should
be rouAssistant Professor,
Surgeryas
/ Emergency
Medicine
however,
that
theasdata
reflected
other
as well
the relatively
inexpensive
costsothere
has been
an ongoing
from global
ischemic insults
and masDrug Administration
has
and Clinical Scholar,
Department
of
Clinical
Sciences
of
treatment
(34
–36).
and
increasing
interest
in
sive
systemic
inflammatory
responses
tinely administered
to all critically ill and ciological and perceptual factors and not
University of Texas Southwestern
Medical
Center be- to devastating focal injury
nal new drugThe
applications
In the following discussion, the ratioidentifying
differences
and apoptoand the Parkland
Health
and
Hospital
persons,
soonsisasin possible
routinely administering
IV estrotween
men
and
womenSystem;
inand
termsas
of their
vital organs (10an
–31).underlying
Further- nale for
physiologic
disadvantage.
ormally study the
use of injured
respective physiologic responses to crit- more, an exogenous infusion of estro- gen to the critically ill and injured will be
Medical Director
for
Resuscitation
Research,
after
onset
of their
specific malady (10, For example,
oned in this Assistant
text.
it was
hypothesized
that
developed
by reviewing
some of the perical illness and injury as well as their
Dallas Metropolitan BioTel (EMS) System, Dallas, Texas, USA gen may not only have a direct
sclosed any potential con- 12,
tinent clinical
observations,
extensive ex- atrelative
rates of survival and recovery therapeutic benefit in some
instances,
29 –33).
perhaps
women
did not
seek medical
(1–9). Among a number of proposed estrogen administration may also be perimental data, and the related safety
What makes
this provocative
and feasibility
of thistheir
treatment.
The dismechanisms
for the identified
differ- synergisticargutention as
or that
symptoms
with other resuscitative
in- readily
ing this article, E-mail:
cussion
will
also
detail
some
of
the
curences,
the
potential
and
powerful
influP
,, M
M
,, M
P
(10, 18, 19,were
22, 27–29,
Paauull E
E.. P
Peeppeement
MD
D,,even
MP
PH
Hmore
MA
AC
C
P,, FFC
CC
CM
Mterventions
persuasive
is the longnot32).recognized as “typical.” At
the
ence of sex hormones has been gaining
A significant body of laboratory evi- rent scientific initiatives related to sex
hormone
therapy,
and
it
will
provide
recsignificant
attention
(2,
10
–12).
Estrostanding,
documented
safety dence,
and simplicof Medicine,
Surgery, Pediatrics,
Public Health
e Society of Professor
Critical Care
sameof species
time, it was also conjectured that
bridging across a variety
gen, in
have protective and a breadth of experimental models, ommendations for future research in
and Riggs Family Chair
in particular,
Emergencymay
Medicine
iams & Wilkins
of a single
dose of IV
estrogen women may not receive interventions as
University of Texasity
Southwestern
Medical Center
now supports the concept that estrogen what is now being called resuscitative
Health and Hospital System,
Dallas, USAillnesses
may be an effective
interven- endocrinology.
for various
and therapeutic
13e3181f243a9and the Parklandadministration
aggressively
as men (37, 40).
ry as well as their
vival and recovery
mber of proposed
e identified differand powerful influs has been gaining
(2, 10 –12). Estromay have protective
O
From the Departments of Internal Medicine (PEP, tion for a spectrum of severe physiologic
Director, City of Dallas
Emergency
Services
forAHI),
AHI),Medical
Surgery (Emergency
Medicine)
(PEP, JGW,
insults and injuries (12–28). Although
Public Safety, Public
Health,
Pediatrics
(PEP),Homeland
and School of Security
Public Healthand
(PEP),Research
The
definitive clinical trials are still lacking,
University of Texas Southwestern Medical Center and
Crit Care
the striking experimental evidence,
as
the Parkland Health and Hospital System, Dallas TX;
and The Dallas Fort Worth Center for Resuscitation
well as several compelling clinical obserResearch (PEP, JGW, AHI), Dallas, TX.
vations have spawned a very convincing
Recent studies, including Wigginton’s
longitudinal,
study of cardiac arrests
Funded, in part,recent
by the National
Institutes population-based
of Health
argument
that intravenous
(IV) estrogen,
(Clinical and
Translational
Award grant
num(n =~10,000 out-of-hospital
subjects)
andScience
Topjian’s
corresponding
in-hospital
registry study
and
perhaps
other
female
sex
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Cohort studies of sex hormone
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MedFemale
2010SexVol.
38, No.
10 (Suppl.)
Hormones
and Cardiac
Arrest. In the mid-1990s there was an existing controversy regarding women having
worse outcomes than men in heart attack
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