PELATIHAN RESUSITASI

PEDIATRIK TAHAP LANJUT

SYOK
KOMISI RESUSITASI PEDIATRIK
UKK PEDIATRI GAWAT DARURAT
IDAI
APRC

DEFINISI SYOK
SINDROM KLINIS AKIBAT KEGAGALAN
SISTEM
SIRKULASI UNTUK MENCUKUPI :

NUTRISI PASOKAN
METABOLISME
OKSIGEN UTILISASI JARINGAN TUBUH

FASE: KOMPENSASI
DEKOMPENSASI
IREVERSIBEL
DEFISIENSI O2 SELULER

Etiologi Syok
Type

Primary Insult

Common Causes

Hypovolemic

Decreased circulating
blood vol
Vasodilation -> venous
pooling -> decreased preload
Obstruction of cardiac

Dehydration, hemorrhage,
capilarry leaks
Sepsis, anaphylaxis,
drug intoxication,
spinal cord injury
Cardiac tamponade,

filling/out flow

pneumothoracx,

Distributive
Obstructive
tension
pulmonary
Cardiogenic

Decreased contractility

Dissociative

O2 not released from

hemoglobin

embolus
Congenital heart disease,
myocarditis, dysritmia
CO poisoning,
methemoglobinemia

FUNGSI SISTEM SIRKULASI

JANTUNG CURAH JANTUNG

METABOLISME
PEMB. DARAH ALIRAN DARAH
ADEKUAT
VOL. DARAH
O2 DELIVERY

METABOLIT

ELIMINASI DI ORGAN PEMBUANGAN

DO2 = CO x CaO2
CaO2 = (1,34 x Hb x sat O2) + (0,003 x PaO2)

JARINGAN

Pengaturan curah jantung dan tekanan

darah

Preload

Contractility

Heart rate

Stroke volume

Cardiac output Systemic vascular resistance

Blood pressure

Afterload

Distribution of CO & VO2

in a Healthy Resting Normal Subject

% Total AVDO2 % Total

Organ CO vol % VO2
GI tract and liver 244.1 25
Skeletal muscle 218.0 30
Kidney 191.3
7
Brain 136.3 20
Skin 91.0
2
Heart 411.4 11
Other organs 103.0
5

Adapted from Wade OL, Bishop JM: Cardiac output and regional blood flow, Oxford, Blackwell, 1

 Extracel. Fluid
Low Output Cardiac Failure
Volume Pericardial Tamponade Oncotic Pressure

Constrictive Pericarditis Capillary Permeability

CARDIAC OUTPUT

Non-osmotic
Vasopressin
Stimulation

RENAL WATER
RETENTION

Intra vasc. Vol. due to

Activation receptor of ventricular & arterial

Stimulation of
Activation of the
Sympathetic Nervous
System

PERIPHERAL & RENAL

ARTERIAL VASC. RESISTANCE

MAINTENANCE OF EFFECTIVE
ARTERIAL BLOOD VOLUME

Renin-AngiotensinAldosterone System

RENAL SODIUM
RETENTION

FRANK STARLING`S LAW

STROKE VOLU ME

SYMPATHOMIMETIC
AMINES
XANTHINES
POSITIVE
GLUCAGON
INOTROPY
CARDIAC GLYCOSIDES
4

D
3
HYPOXEMIA
ACIDOSIS
HYPOGLYCEMIA
ENDOTOXEMIA
2
DRUG TOXICITY

C
B
NEGATIVE
INOTROPY

A
VOLUME INFUSION
0

10

CENTRAL VENOUS PRESSURE (Toor)

Oxyhemoglobin saturation

The Oxygen-hemoglobin Dissociation Curve

H+
2,3-DPG
CO2
Pi
H+
2,3-DPG
CO2
Pi

PaO2

Shock

Hypotension

Preload

Intravasculer volume
Myocardial contractility
Anaerobic metabolism

Membrane permeability

Cellular hypoxia

Metabolic by-products:
- lactic acid
- myocardial depressant factor
- endogeneous catecholamines
- adenine nucleotides

STADIUM SYOK
KOMPENSASI
DEKOMPENSASI
IREVERSIBEL (PRETERMINAL)
PERJALANAN KLINIS BERSIFAT
PROGRESIF

FASE I: KOMPENSASI
KOMPENSASI TEMPORER
SIMPATIS, SVR, TEKANAN NADI
DISTRIBUSI SELEKTIF ALIRAN DARAH
RETENSI NA & AIR
KLINIS :
* TAKHIKARDIA

* GADUH GELISAH
* KULIT PUCAT DINGIN
* PENGISIAN KAPILER >>

FASE 2: DEKOMPENSASI
KOMPENSASI MULAI GAGAL
HIPOPERFUSI HIPOKSIA JAR. METAB.
ANAEROBIK
GGN. METAB. SELULER
PELEPASAN MEDIATOR : * VASODILATASI
* PERMEABILITAS
* DEPRESI MIOKARD
* GGN KOAGULASI

KLINIS :

TAKHIKARDIA
TEKANAN DARAH TAKIPNU
PERFUSI PERIFER ASIDOSIS (+) OLIGURI (+)
TINGKAT KESADARAN

FASE 3: IREVERSIBEL
KOMPENSASI GAGAL
CADANGAN ENERGI TUBUH
KERUSAKAN/KEMATIAN SEL DISFUNGSI
ORGAN
MULTIPEL
KLINIS : * T.D TAK TERUKUR * NADI TAK TERABA
* TINGKAT KESADARAN * ANURIA (+)
* GAGAL MULTI ORGAN
DAN KEMATIAN

Manifestasi Klinis Syok

Clinical Signs

Compensated Uncompensated

Blood loss (%)

Up to 25

25 - 40

Irreversible

> 40

Heart rate
Tachycardia + Tachycardia ++
Tachy/bradycardia
Systolic BP N N or falling
Plummeting
Pulse volume N/
+ ++
Capillary refill
N/
+ ++
Skin
Cool, pale Cold, mottled
Cold, deathly pale
Respiratory rate Tachypnoea + Tachypnoea ++
Sighing rsp.
Mental state
Mild agitation Lethargic Reacts only to pain
Uncooperative or unresponsive

GANGGUAN PERFUSI
PERIFER
CORE > PERIFER TEMP. ~ > 2O C
CAPILLARY REFILL >> :
* NAIL BED PRESS
* BLANCHING SKIN TEST

PRODUKSI URIN
(N) BAYI = 2 ml/kg/jam
ANAK = 1 ml/kg/jam

TATALAKSANA RESUSITASI
SYOK
RESUSITASI AWAL
OKSIGEN 100% + VENTILATORY SUPPORT
PASANG AKSES VASKULER (90 DETIK)
FLUID CHALLENGE (20 ml/kg BB)
SECEPATNYA < 10 MENIT
DPT DIULANGI 2-3 KALI
KRISTALOID/KOLOID
PEMANTAUAN AWAL
RESPON THD FLUID CHALLENGE
PANTAU PROD. URIN (KATETER)
STAT. LAB/PENUNJANG

Monitoring
State of consiousness-Glasgow Coma Scale
Respiratory rate and character
Cardiovascular parameters

Skin and core temperature difference

Pulse rate and volume
Blood pressure
Capillary perfusion time
Central venous pressure - should be monitored
in a patient where there has been poor response
to fluid therapy or with established shock.

Urinary output - urine bag, or preferably

catheter; output should be 1-2 ml/kg body
weight
Pulse oximetry

RESUSITASI LANJUT
BILA FLUID CHALLENGE NON
RESPONSIVE
INTUBASI & VENT. MEKANIK
PASANG CVP & LOADING HATI-HATI
KOREKSI EFEK INOTROPIK NEGATIF
Hb < 5 g/dl PRC 10 ml/kg BB (Ht 40-50
vol %)

OBAT INOTROPIK

PEMANTAUAN LANJUT
CARI PENYEBAB SYOK (CXR,
KONSULTASI)
EVALUASI FUNGSI SIST. ORGAN LAIN :
ATN/PRE RENAL FAILURE
ARDS
CARDIAC FUNCTION
GGN. KOAGULASI/DIC
ORGAN-ORGAN LAIN

CHILD IN SHOCK

(1) OXYGEN

(2) CRYSTALLOID
20 ml/kg)
NO IMPROVEMENT

NO IMPROVEMENT

URINARY CATHETER

(3) CRYSTALLOID
- INCREASE MABP
(20 ml/kg)
- NORMALIZATION HR
- IMPROVED PERFUSION
- URINE OUTPUT > 1 ml/kg/hr

ESTABLISH CVP

CVP < 5 Torr

CRYSTALLOID INFUSION
UNTIL CVP - 5 Torr

IMPROVEMENT

ESTABLISH ETIOLOGY
CONFIRM SOURCE
OF FLUID LOSS

IMPROVEMENT

ESTABLISH ETIOLOGY,
ETIOLOGY,
OBSERVATION
CVP > 5 Torr
NO IMPROVEMENT

ABG, HT, NaK, GLUC Ca,

SWAN GANZ CATHETER
CO, RAP, PAP, POAP

STROKE VOLUME

1. CORRECT
ACIDOSIS
2. Co. GLUCOSE
3. INTROPIC
SUPPORT

CENTRAL VENOUS PRESSURE

Stop
pemberian

Le Veen HH: Surg Gynecol Obstet 1980; 150:139-149

Stadium syok septik dan manifestasi klinis

Stadium

Warm Shock
perfusi perifer (N)
Smv O2
(Hiperdinamik)kulit hangat kering
VO2
HR nadi bounding
CO
suhu / (tak stabil)
SVR
RR , gg. kesadaran

hipokarbia
hopoxia
kadar laktat
hiperglikemia

Cold Shock
sianosis
(Hipodinamik) kulit dingin lembab
nadi kecil, lemah
HR , Oliguria
shallow breathing
pe kesadaran

hipoxia
asidosis metab
koagulopati
hipoglikemi

MOSF

failure

Tanda Klinis

bergantung sistem
yang terkena

Gang fisiologis

CO
SVR
CVP
Smv O2

Biokimiawi

Koma
susai
ARDS, CHF, RF
GI bleeding/DIC

jenis
organ

TATALAKSANA SYOK SEPTIK

AB BROAD SPECTRUM
SESUAI
KULTUR
RESUSITASI CAIRAN : KOLOID/KRISTALOID
OBAT INOTROPIK : DOBUTAMIN + DOPAMIN
ISOPRENALIN/ADRENALIN

SVR VASODILATASI PERIFER

KOREKSI : - HIPO/HIPERGLIKEMI
- ASAM BASA
- ELEKTROLIT

TATALAKSANA SYOK
ANAFILAKTIK
STOP ALERGEN PENYEBAB + ADRENALIN (IM)
AIR WAY & RESPIRATION ADEKUAT
WHEEZING NEBULASI
ADRENALIN/SALBUTAMOL
OBSTRUKSI INTUBASI/SURGICAL AIRWAY
SIRKULASI & HEMODINAMIK
VASO PRESOR
: ADRENALIN (10 g/kg BB)
FLUID LOADING
: KRISTALOID (20 ml/kg
BB/IV-IO)
RE ASSESSMENT ABC RESUSITASI
WHEEZING (+)
NEBULASI SALBUTAMOL
BILA PERLU
(+) HIDROKORTISON (IV)
(+) AMINOPILIN/SALBUTAMOL DRIP
SYOK BERLANJUT :
KOLOID + INOTROPIK

TATALAKSANA SYOK
KARDIOGENIK
OKSIGENISASI ADEKUAT
KOREKSI GGN ASAM BASA & ELEKTROLIT
KURANGI RASA SAKIT & ANSIETAS
ATASI DISRITMIA JANTUNG
KELEBIHAN PRELOAD : DIURETIKA
KONTRAKTILITAS:FLUID CHALLENGE SESUAI
CVP/POAP
OBAT INOTROPIK (+)

BEBAN AFTERLOAD (SVR ) : VASODILATOR

KOREKSI PENYEBAB PRIMER

Key points in
management
Remember BP and pulse are unreliable
indicators in early septic shock
Look for minor degrees of mental impairment
(anxiety, restlessness)
Do not delay treatment, try to prevent the onset
of hypotension, metabolic acidosis, and hypoxia
Give adequate fluids early in treatment,
especially colloids
Do not use inotropic agents until the patient has
received adequate fluid therapy
Monitor blood glucose, gases, and pH, and treat
appropriately

SEQUENCE OF THERAPEUTIC MANEUVERS

(VIPPS)
Priority Mnemonic Therapy
Purpose
1
V Ventilate Adequate O2&CO2
exchange
2
I Infuse
Vascular Access
Blood, fluid &
electrolite balance
3
P Pump
Restoration cardiac
performance
4
P Pharmacologic
Improved
perfusion
by vasoactive agents
5
S Specific/ Medical & surgical
Surgical management of
primary causes

Pediatric Shock

Lou DeNicola, M.D.

Professor, Pediatric Critical
Care
University of
Florida/Jacksonville

Linda Siegel, M.D.

Assistant Professor, Pediatric
Critical Care
Mount Sinai School of
Medicine

Introduction
Shock is a syndrome that results
from inadequate oxygen delivery to
meet metabolic demands
DO2 < VO2
Untreated this leads to metabolic
acidosis, organ dysfunction and
death

Oxygen Delivery
Oxygen delivery = Cardiac Output x
Arterial Oxygen Content
(DO2 = CO x CaO2)

Cardiac Output = Heart Rate x Stroke

Volume
(CO = HR x SV)
SV determined by preload, afterload and
contractility

Art Oxygen Content = Oxygen content

of the RBC + the oxygen dissolved in
plasma
(CaO2 = Hb X SaO2 X 1.34 + (.003 X PaO2)

Stages of Shock

Compensated

Uncompensated

Vital organ function maintained, BP

remains normal.
Microvascular perfusion becomes
marginal. Organ and cellular function
deteriorate. Hypotension develops.

Irreversible

Compensatory
Mechanisms

Baroreceptors

In aortic arch and carotid sinus, stimulated by high MAP

and then excite cardioinhibitory center leading to
vasodilation, decreased BP, HR and CO. Hyotension will lift
the stimulation and result in vasoconstriction, increased
HR, BP and CO.

Chemoreceptors

Respond to cellular acidosis and results in vasoconstriction

and respiratory stimulation.

Compensatory Mechanisms
(cont)
Renin-angiotensin system
Decreased perfusion to the kidney leads to
renin secretion. Renin is eventually
converted to Anigiotensin II leading to
vasoconstriction and aldosterone release.
Aldosterone leads to sodium and water
reabsorption
Humoral responses
catecholamine release leading to increased
contractility and vasoconstriction.
Autotransfusion
Reabsorption of interstitial fluid.

Clinical Presentation
Early diagnosis requires a
index of suspicion

high

Diagnosis is made through the physical

examination focused on tissue perfusion
Abject hypotension is a late and
premorbid sign

Hemodynamic Response to
Hemorrhage
% of

Vasc Resistance

Control

100

Blood Pressure
Cardiac Output

25%

50%

% Plasma Loss

Initial Evaluation: Physical

Exam
Neurological: Fluctuating mental
status, sunken fontanel
Skin and extremities: Cool,
pallor, mottling, cyanosis, poor cap
refill, weak pulses, poor muscle
tone.
Cardio-pulmonary: Hyperpnea,
tachycardia.
Renal: Scant, concentrated urine

Initial Evaluation: Directed

History
Past

medical history
heart disease
surgeries
steroid use
medical problems
Brief history of present
illness
exposures

Differential Diagnosis of Shock I

Hypovolemic
Hemorrhage
Serum/Plasma loss
Drugs

Distributive
Analphylactic
Neurogenic
Septic

Cardiogenic
Myocardial
Dysrrhythmia
CHD-(duct
dependant)

Obstructive
Pneumo,
Tamponade,
Dissection

Dissociative
Heat, CO, Cyanide
Endocrine

Differential Diagnosis of Shock

II
Precise
Precise etiologic
etiologicclassification
classificationmay
may
be delayed
delayed
Immediate
Immediate treatment
treatmentisisessential
essential
Absolute
Absolute or
or relative
relativehypovolemia
hypovolemiaisis
usually
usually present
present
The
The size
size of
of the
thecardiac
cardiacsilhouette
silhouetteon
plain
filmfilm
can can
be used
to estimate
on plain
be used
to
the
need for
replacement.
estimate
thevolume
need for
volume
replacement.

Neonate in Shock:
Include in differential:
Congenital adrenal hyperplasia
Inborn errors of metabolism
Obstructive left sided cardiac
lesions:
Aortic stenosis
Hypoplastic left heart syndrome
Coarctation of the aorta
Interrupted aortic arch

Outcome of Pediatric
Shock
Chang 1999

2 2 S h o c k K id s
1 1 S e p t ic

7 H y p o v o l e m ic

4 C a r d i o g e n ic

8 2 % D ie d

0 % D ie d

7 5 % D ie d

Management-General
Goal: increase oxygen delivery and
decrease oxygen demand:
Oxygen
Fluid
Temperature control
Antibiotics
Correct metabolic abnormalities
Inotropes

Management-General
(cont)
Airway
If not protected or unable to be
maintained, intubate.
Breathing
Always give 100% oxygen to start
Sat monitor
Circulation
Establish IV access rapidly
CR monitor and frequent BP

Management-General
(cont)
Laboratory studies:
ABG
Blood sugar
Electrolytes
CBC
PT/PTT
Type and cross
Cultures

Management-Volume
Expansion
Optimize preload
NS or RL
Except for myocardial failure use 1020cc/kg aliquots q 2-10 minutes
At 40-60cc/kg reassess and consider:
ongoing losses, adrenal, intestinal
ischemia, obstructive shock. Get CXR.
Consider colloid
Further fluid therapy guided by
response, labs, possibly CVP, CXR

Fluid in early septic shock

Carcillo, et al, JAMA, 1991

Retrospective review of 34 pediatric patients with culture +

septic shock, from 1982-1989.
Hypovolemia determined by PCWP, u.o and hypotension.
Overall, patients received 33 cc/kg at 1 hour and 95 cc/kg at 6
hours.
Three groups:

1: received up to 20 cc/kg in 1st 1 hour

2: received 20-40 cc/kg in 1st hour
3: received greater than 40 cc/kg in 1st hour

No difference in ARDS between the 3 groups

Fluid
Fluid in
in early
early septic
septic shock
shock
Carcillo,
Carcillo, et
et al,
al, JAMA,
JAMA, 1991
1991

Group
1

Group
2

Group
3

(n = 14)

(n = 11)

(n = 9)

Hypovolemic
at 6 hours
-Deaths

Not
hypovolemic
at 6 hours
-Deaths

Total deaths

Management - Cardiotonics
I
Lack of history of fluid losses, history of
heart disease, hepatomegaly, rales,
cardiomegaly and failure to improve
perfusion with adequate oxygenation,
ventilation, heart rate, and volume
expansion suggests a cardiogenic or
distributive component.
Prior to introduction of cardiotonics, the
goals of therapy and criteria for
monitoring of endpoint should be
established

Management - Cardiotonics
II
Epinephrine
0.05-1.5 ug/kg/min
increase HR, SVR,
contractility
End point: adequate BP;
acceptable tachycardia

Norepinephrine
0.05-1.0 ug/kg/min
Increase SVR
End point: adequate BP

Dopamine
2-20 ug/kg/min
Lower doses,
increases renal and
splanchnic blood
flow, & contractility.
Higher doses
increases HR and
SVR
End Point: Improved
perfusion, BP, Urine

Management - Cardiotonics
III
Dobutamine
1-20 ug/kg/min
increases
contractility, may
reduce SVR, PVR
End Point: Improved
perfusion, may
decrease BP

Prostaglandin E1
0.05-0.1 ug/kg/min
maintains patency
of ductus

Hypovolemic Shock
Most common form of shock worldwide
Results in decreased circulating
blood volume, decrease in prelaod,
decreased stroke volume and
resultant decrease in C.O.
Etiology: Hemorrhage, renal and/or
GI fluid losses, capillary leak
syndromes

Hypovolemic Shock
Clinically, history of
vomiting/diarrhea or trauma/blood
loss
Signs of dehydration: mucous
membranes, tears, skin turgor
Hypotension, tachycardia without
signs of congestive heart failure

Hemorrhagic Shock
Most common cause of shock in
the United States (due to trauma)
Patients present with an obvious
history (but in child abuse history
may be misleading)
Site of blood loss obvious or
concealed (liver,
spleen,intracranial, GI)
Hypotension, tachycardia and

Hypovolemic/Hemorrhagic
Shock: Therapy
Always begin with ABCs
Replace circulating blood volume
rapidly: start with
crystalloid/colloid
Blood products as soon as
available for hemorrhagic shock
(Type and Cross with first blood
draw)
Replace ongoing fluid/blood losses

Septic Shock
SIRS/Sepsis/Septic shock

Mediator release:
exogenous & endogenous

Maldistribution

Cardiac

of blood flow

dysfunction

Imbalance of
oxygen
supply and
demand

Alterations in
metabolism

Outcomes of mediator release in systemic inflammatory response

syndrome (SIRS), sepsis, and septic shock

Septic Shock: Warm

Shock
Early, compensated, hyperdynamic state
Clinical signs
Warm extremities with bounding pulses,
tachycardia, tachypnea, confusion.
Physiologic parameters
widened pulse pressure, increased cardiac
ouptut and mixed venous saturation,
decreased systemic vascular resistance.
Biochemical evidence:
Hypocarbia, elevated lactate, hyperglycemia

Septic Shock: Cold

Shock
Late, uncompensated stage with drop in cardiac
output.
Clinical signs
Cyanosis, cold and clammy skin, rapid, thready
pulses, shallow respirations.
Physiologic parameters
Decreased mixed venous sats, cardiac output
and CVP, increased SVR, thrombocytopenia,
oliguria, myocardial dysfunction, capillary leak
Biochemical abnormalities
Metabolic acidosis, hypoxia, coagulopathy,
hypoglycemia.

Septic Shock (cont)

Cold Shock rapidly progresses to

MOSF or death, if untreated
Multi-Organ System Failure: Coma,
ARDS, CHF, Renal Failure, Ileus or GI
hemorrhage, DIC
More organ systems involved, worse
the prognosis
Therapy: ABCs, fluid
Appropriate antibiotics, treatment of
underlying cause

Cardiogenic Shock
Etiology:
Dysrhythmias
Infection
Metabolic
Obstructive
Drug intoxication
Congenital heart disease
Trauma

Cardiogenic Shock (cont)

Differentiation from other types of
shock:

History
PE:
Enlarged liver
Gallop rhythm
Murmur
Rales

CXR:
Enlarged heart, pulmonary venous congestion

Cardiogenic Shock (cont)

Management:
Improve cardiac output::

Correct dysrhymias
Optimize preload
Improve contractility
Reduce afterload
Minimize cardiac work:

Maintain normal temperature

Sedation
Intubation and mechanical ventilation
Correct anemia

Distributive Shock
Due to an abnormality in vascular tone
leading to peripheral pooling of blood
with a relative hypovolemia.
Etiology

Anaphylaxis
Drug toxicity
Neurologic injury
Early sepsis

Management

Fluid
Treat underlying cause

Obstructive Shock

Mechanical obstruction to ventricular

outflow
Etiology: CHD, massive PE, tension
pneumothorax, cardiac tamponade
Inadequate C.O. in the face of
adequate preload and contractility
Tamponade: Narrow pulse pressure
and/or EMD
Treat underlying cause.

Dissociative Shock

Inability of Hemoglobin molecule to

give up the oxygen to tissues
Etiology: Carbon Monoxide poisoning,
methemoglobinemia,dyshemoglobine
mias
Tissue perfusion is adequate, but
oxygen release to tissue is abnormal
Early recognition and treatment of
the cause is main therapy

Hemodynamic Variables
in Different Shock States
Hypovolemi
c
Cardiogeni
c
Obstructive
Distributiv
e
Septic:
Early
Septic:
Late

CO

SVR

MAP
Or
Or
Or
Or
Or

Wedg
e

Or

CVP

Or

or

Final Thoughts
Recognize compensated shock quickly- have a
high index of suspicion, remember tachycardia is
first sign. Hypotension is late and ominous.
Gain access quickly- if necessary use an IO line.
Administer adequate amounts of fluid rapidly.
Remember ongoing losses.
Correct electrloytes and glucose problems quickly.
If the patient is not responding the way you think
he should, broaden your differential, think about
different types of shock.

Figure 1.

FACTORS AFFECTING OXYGEN DELIVERY

Hgb

CaO2

A-a gradient
DPG
Acid-Base Balance
Blockers
Competitors
Temperature

Influenced By

Oxygenation
DO2
Influenced By

Drugs
Conduction System

HR
CO

EDV
SV

CVP
Venous Volume
Venous Tone

Ventricular
Compliance
Influenced By

ESV

Contractility

Influenced By

Afterload
Temperature
Drugs

Metabolic Milieu
Ions
Acid Base
Temperature
Drugs
Toxins
Blockers
Competitors
Autonomic Tone